bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat
Authors: Zong Shaohui , Zeng Gaofeng , Fang Ye , Peng Jinzhen , Tao Yong , Li Keke , Zhao Jingmin
Published: April 2014

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.
Comparison of Physicochemical Properties of Nano‐ and Microsized Crystals in the Urine of Calcium Oxalate Stone Patients and Control Subjects
Authors: Gao Jie , Xue Jun-Fa , Xu Meng , Gui Bao-Song , Wang Feng-Xin , Ouyang Jian-Ming
Published: April 2014

Purpose. To compare the properties of different sizes of urinary crystallites between calcium oxalate (CaOx) calculi patients and healthy controls. Methods. We studied the average particle size, size distribution, intensity‐autocorrelation curve, zeta potential (ζ), conductivity, mobility, aggregation state, and stability of different sizes of urinary crystallites by nanoparticle size analysis and transmission electron microscopy after filtration through a microporous membrane with an aperture size from 0.22 μm to 0.45, 1.2, 3, and 10 μm. Results. The urinary crystallites of the CaOx calculi patients were uneven and much easy to aggregate than those of controls. The number of large‐sized crystallites of the patients was significantly more than that of the controls. The main components of the nanosized urinary crystallites in patients were CaOx monohydrate (COM), uric acid, and β‐calcium phosphate, and these components were basically similar to those of the microsized urinary crystallites. The urinary crystallites of the calculi patients were easier to aggregate than that of the controls, and the small‐sized urinary crystallites were much easier to agglomerate. Conclusions. The urinary system of CaOx calculi patients is unstable and highly susceptible to urinary crystallite aggregation. The rapid aggregation of urinary crystallites may be the key factor affecting urolithiasis formation.
Modeling of the Transport Phenomena in Passive Direct Methanol Fuel Cells Using a Two-Phase Anisotropic Model
Authors: Miao Zheng , Xu Jin-Liang , He Ya-Ling
Published: April 2014

The transport phenomena in a passive direct methanol fuel cell (DMFC) were numerically simulated by the proposed two-dimensional two-phase nonisothermal mass transport model. The anisotropic transport characteristic and deformation of the gas diffusion layer (GDL) were considered in this model. The natural convection boundary conditions were adopted for the transport of methanol, oxygen, and heat at the GDL outer surface. The effect of methanol concentration in the reservoir on cell performance was examined. The distribution of multiphysical fields in the membrane electrode assembly (MEA), especially in the catalyst layers (CLs), was obtained and analyzed. The results indicated that transport resistance for the methanol mainly existed in the MEA while that for oxygen and heat was primarily due to natural convection at the GDL outer surface. Because of the relatively high methanol concentration, the local reaction rate in CLs was mainly determined by the overpotential. Methanol concentration between 3 M and 4 M was recommended for passive liquid feed DMFC in order to achieve a balance between the cell performance and the methanol crossover.
Numerical Investigations on the Slag Eye in Steel Ladles
Authors: Liu Yan-He , He Zhu , Pan Li-Ping
Published: April 2014

A numerical model has been developed to analyze the transient three-dimensional and three-phase flow in a bottom stirring ladle with a centered porous plug, which takes into account the steel, gas, and slag phases; it enables us to predict the fluid flow and heat transfer in the very important steel/slag region. The numerical results of the present model show that the obtained relationship between nondimensional areas of slag eye and the Froude number is in good agreement with the reported data.
Degree of Approximation of Functionsf~∈HωClass by the(Np·E1)Means in the Hölder Metric
Authors: Mishra Vishnu Narayan , Khatri Kejal
Published: April 2014

A new estimate for the degree of approximation of a functionf˜∈Hωclass by(Np·E1)means of its Fourier series has been determined. Here, we extend the results of Singh and Mahajan (2008) which in turn generalize the result of Lal and Yadav (2001). Some corollaries have also been deduced from our main theorem.
Development and Retranslational Validation of anIn VitroModel to Characterize Acute Infections in Large Human Joints
Authors: Pilz Ingo H. , Mehlhorn Alexander , Dovi-Akue David , Langenmair Elia Raoul , Südkamp Norbert P. , Schmal Hagen
Published: April 2014

Bacterial infections can destroy cartilage integrity, resulting in osteoarthritis. Goal was to develop anin vitromodel within vivovalidation of acute joint inflammation. Inflammation in cocultivated human synovial fibroblasts (SFB), chondrocytes (CHDR), and mononuclear cells (MNC) was successively relieved for 10 days. Articular effusions from patients with (n=7) and without (n=5) postoperative joint infection in healthy patients (ASA 1-2) were used as model validation. Inflammationin vitroresulted in an enormous increase in IL-1 and a successive reduction in SFB numbers. CHDR however, maintained metabolic activity and proteoglycan synthesis. While concentrations of bFGFin vivoandin vitrorose consistently, the mRNA increase was only moderate. Concurring with ourin vivodata, cartilage-specific IGF-1 steadily increased, while IGF-1 mRNA in the CHDR and SFB did not correlate with protein levels. Similarly, aggrecan (ACAN) protein concentrations increasedin vivoand failed to correlatein vitrowith gene expression in either the CHDR or the SFB, indicating extracellular matrix breakdown. Anabolic cartilage-specific BMP-7 with highly significant intra-articular levels was significantly elevatedin vitroon day 10 following maximum inflammation. Ourin vitromodel enables us to validate early inflammation ofin vivocell- and cytokine-specific regulatory patterns. This trial is registered with MISSinG, DRKS00003536.
Day‐to‐Day Scheduling Travel Time Adjustment Behavior and Simulation
Authors: Li Hua-Min , Wang David Z. W. , Huang Hai-Jun , Yu Xiao-Jun
Published: April 2014

This paper proposes a modeling framework to study the day‐to‐day scheduling travel time adjustment behavior on the base of past experiences. Scheduling travel time is defined as the difference between the requested arrival time and the departure time. Mathematical equations are established to formulate every traveler’s dynamic adjustment on his/her departure time. In the adjustment process, the last day’s scheduling time is an essential component, while the numbers of late arrivals, punctual arrivals, and early arrivals in a previous day are used to reflect the past experiences. Simulation results are presented to illustrate the effectiveness of the proposed modeling framework.
The Role of Dendritic Cells in Tissue-Specific Autoimmunity
Authors: Mbongue Jacques , Nicholas Dequina , Firek Anthony , Langridge William
Published: April 2014

In this review, we explore the role of dendritic cell subsets in the development of tissue-specific autoimmune diseases. From the increasing list of dendritic cell subclasses, it is becoming clear that we are only at the beginning of understanding the role of these antigen presenting cells in mediating autoimmunity. Emerging research areas for the study of dendritic cell involvement in the onset and inhibition of tissue-specific autoimmunity are presented. Further, we compare tissue specific to systemic autoimmunity to demonstrate how development of dendritic cell-based therapies may be broadly applicable to both classes of autoimmunity. Continued development of these research areas will lead us closer to clinical assessment of novel immunosuppressive therapy for the reversal and prevention of tissue-specific autoimmunity. Through description of dendritic cell functions in the modulation of tissue-specific autoimmunity, we hope to stimulate a greater appreciation and understanding of the role dendritic cells play in the development and treatment of autoimmunity.
Mechanism and Design Analysis of Articulated Ankle Foot Orthoses for Drop-Foot
Authors: Alam Morshed , Choudhury Imtiaz Ahmed , Mamat Azuddin Bin
Published: April 2014

Robotic technologies are being employed increasingly in the treatment of lower limb disabilities. Individuals suffering from stroke and other neurological disorders often experience inadequate dorsiflexion during swing phase of the gait cycle due to dorsiflexor muscle weakness. This type of pathological gait, mostly known as drop-foot gait, has two major complications, foot-slap during loading response and toe-drag during swing. Ankle foot orthotic (AFO) devices are mostly prescribed to resolve these complications. Existing AFOs are designed with or without articulated joint with various motion control elements like springs, dampers, four-bar mechanism, series elastic actuator, and so forth. This paper examines various AFO designs for drop-foot, discusses the mechanism, and identifies limitations and remaining design challenges. Along with two commercially available AFOs some designs possess promising prospective to be used as daily-wear device. However, the design and mechanism of AFO must ensure compactness, light weight, low noise, and high efficiency. These entailments present significant engineering challenges to develop a new design with wide consumer adoption.
Derivative‐Based Trapezoid Rule for the Riemann‐Stieltjes Integral
Authors: Zhao Weijing , Zhang Zhaoning
Published: April 2014

The derivative‐based trapezoid rule for the Riemann‐Stieltjes integral is presented which uses 2 derivative values at the endpoints. This kind of quadrature rule obtains an increase of two orders of precision over the trapezoid rule for the Riemann‐Stieltjes integral and the error term is investigated. At last, the rationality of the generalization of derivative‐based trapezoid rule for Riemann‐Stieltjes integral is demonstrated.
In Silico Investigation of Potential PARP‐1 Inhibitors from Traditional Chinese Medicine
Authors: Chen Kuan-Chung , Sun Mao-Feng , Chen Calvin Yu-Chian
Published: April 2014

Poly(ADP‐ribose) polymerases (PARPs) are nuclear enzymes which catalyze the poly‐ADP‐ribosylation involved in gene transcription, DNA damage repair, and cell‐death signaling. As PARP‐1 protein contains a DNA‐binding domain, which can bind to DNA strand breaks and repair the damaged DNA over a low basal level, the inhibitors of poly(ADP‐ribose) polymerase 1 (PARP‐1) have been indicated as the agents treated for cancer. This study employed the compounds from TCM Database@Taiwan to identify the potential PARP‐1 inhibitors from the vast repertoire of TCM compounds. The binding affinities of the potential TCM compounds were also predicted utilized several distinct scoring functions. Molecular dynamics simulations were performed to optimize the result of docking simulation and analyze the stability of interactions between protein and ligand. The top TCM candidates, isopraeroside IV, picrasidine M, and aurantiamide acetate, had higher potent binding affinities than control, A927929. They have stable H‐bonds with residues Gly202 and, Ser243 as A927929 and stable H‐bonds with residues Asp105, Tyr228, and His248 in the other side of the binding domain, which may strengthen and stabilize ligand inside the binding domain of PARP‐1 protein. Hence, we propose isopraeroside IV and aurantiamide acetate as potential lead compounds for further study in drug development process with the PARP‐1 protein.
Geriatric Hip Fractures and Inpatient Services: Predicting Hospital Charges Using the ASA Score
Authors: Thakore Rachel V. , Lee Young M. , Sathiyakumar Vasanth , Obremskey William T. , Sethi Manish K.
Published: April 2014

Purpose.To determine if the American Society of Anesthesiologist (ASA) score can be used to predict hospital charges for inpatient services.Materials and Methods.A retrospective chart review was conducted at a level I trauma center on 547 patients over the age of 60 who presented with a hip fracture and required operative fixation. Hospital charges associated with inpatient and postoperative services were organized within six categories of care. Analysis of variance and a linear regression model were performed to compare preoperative ASA scores with charges and inpatient services.Results.Inpatient and postoperative charges and services were significantly associated with patients’ ASA scores. Patients with an ASA score of 4 had the highest average inpatient charges of services of $15,555, compared to $10,923 for patients with an ASA score of 2. Patients with an ASA score of 4 had an average of 45.3 hospital services compared to 24.1 for patients with a score of 2.Conclusions.A patient’s ASA score is associated with total and specific hospital charges related to inpatient services. The findings of this study will allow payers to identify the major cost drivers for inpatient services based on a hip fracture patient’s preoperative physical status.
Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland
Authors: Rohde Kristian , Møller Morten , Rath Martin Fredensborg
Published: April 2014

Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent,Aanatgene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction ofAanattranscription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specificAanatexpression. Based on recent advances in our understanding ofCrxin the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specificAanatexpression and by facilitating cAMP response element-based circadian melatonin production.
Commercial Bank Efficiency Evaluation in Consideration of the Undesirable Output and Its Link with Stakeholders Relationship: An Application of China’s Commercial Banks
Authors: Ji Jianyue , Wang Yanxia
Published: April 2014

Based on the modern contract theory, expectancy theory, and stakeholder theory, this paper analyzes how stakeholders relationship influences the efficiency of commercial banks and finds that the efficiency is a function of stakeholders relationship. A DEA model with Seiford′s linear transformation function is developed to evaluate the efficiency in consideration of the undesirable output. The panel Tobit model is established to conduct empirical research with data of 14 Chinese commercial banks from 2004 to 2012. The study finds that except for business customer relation, stakeholder relationship is the key variable that influences comprehensive efficiency of commercial banks.
Analysis of Scalar Field Cosmology with Phase Space Deformations
Authors: Perez-Payan Sinuhe , Sabido M. , Mena E. , Yee-Romero C.
Published: April 2014

Phase space deformations on scalar field cosmology are studied. The deformation is introduced by modifying the symplectic structure of the minisuperspace variables. The effects of the deformation are studied in the “C-frame” and the “NC-frame.” In order to remove the ambiguities of working on different frames, a new principle is introduced. When we impose that both frames should be physically equivalent, we conclude that the only possibility for this model, is to have an effective cosmological constantΛeff≥0. Finally we bound the parameter space forθandβ.
Modeling and Monitoring Terrestrial Primary Production in a Changing Global Environment: Toward a Multiscale Synthesis of Observation and Simulation
Authors: Pan Shufen , Tian Hanqin , Dangal Shree R. S. , Ouyang Zhiyun , Tao Bo , Ren Wei , Lu Chaoqun , Running Steven
Published: April 2014

There is a critical need to monitor and predict terrestrial primary production, the key indicator of ecosystem functioning, in a changing global environment. Here we provide a brief review of three major approaches to monitoring and predicting terrestrial primary production: (1) ground-based field measurements, (2) satellite-based observations, and (3) process-based ecosystem modelling. Much uncertainty exists in the multi-approach estimations of terrestrial gross primary production (GPP) and net primary production (NPP). To improve the capacity of model simulation and prediction, it is essential to evaluate ecosystem models against ground and satellite-based measurements and observations. As a case, we have shown the performance of the dynamic land ecosystem model (DLEM) at various scales from site to region to global. We also discuss how terrestrial primary production might respond to climate change and increasing atmospheric CO2and uncertainties associated with model and data. Further progress in monitoring and predicting terrestrial primary production requires a multiscale synthesis of observations and model simulations. In the Anthropocene era in which human activity has indeed changed the Earth’s biosphere, therefore, it is essential to incorporate the socioeconomic component into terrestrial ecosystem models for accurately estimating and predicting terrestrial primary production in a changing global environment.
Moving Target Detection and Active Tracking with a Multicamera Network
Authors: Zhao Long , Liu Li Fei , Wang Qing Yun , Li Tie Jun , Zhou Jian Hua
Published: April 2014

We propose a systematic framework for Intelligence Video Surveillance System (IVSS) with a multicamera network. The proposed framework consists of low-cost static and PTZ cameras, target detection and tracking algorithms, and a low-cost PTZ camera feedback control algorithm based on target information. The target detection and tracking is realized by fixed cameras using a moving target detection and tracking algorithm; the PTZ camera is manoeuvred to actively track the target from the tracking results of the static camera. The experiments are carried out using practical surveillance system data, and the experimental results show that the systematic framework and algorithms presented in this paper are efficient.
Old Drug New Use—Amoxapine and Its Metabolites as Potent Bacterial β-Glucuronidase Inhibitors for Alleviating Cancer Drug Toxicity
Authors: Kong Ren , Liu Timothy , Zhu Xiaoping , Ahmad Syed , Williams Alfred L. , Phan Alexandria T. , Zhao Hong , Scott John E. , Yeh Li-An , Wong Stephen T.C.
Published: April 2014

Purpose: Irinotecan (CPT-11) induced diarrhea occurs frequently in patients with cancer and limits its usage. Bacteria β-glucuronidase (GUS) enzymes in intestines convert the nontoxic metabolite of CPT-11, SN-38G, to toxic SN-38, and finally lead to damage of intestinal epithelial cells and diarrhea. We previously reported amoxapine as a potent GUS inhibitor in vitro. To further understand the molecular mechanism of amoxapine and its potential for treatment of CPT-11–induced diarrhea, we studied the binding modes of amoxapine and its metabolites by docking and molecular dynamics simulation, and tested the in vivo efficacy on mice in combination with CPT-11.

Experimental Design: The binding of amoxapine, its metabolites, 7-hydroxyamoxapine and 8-hydroxyamoxapine, and a control drug loxapine with GUS was explored by computational protocols. The in vitro potencies of metabolites were measured by Escherichia coli GUS enzyme and cell-based assay. Low-dosage daily oral administration was designed to use along with CPT-11 to treat tumor-bearing mice.

Results: Computational modeling results indicated that amoxapine and its metabolites bound in the active site of GUS and satisfied critical pharmacophore features: aromatic features near bacterial loop residue F365′ and hydrogen bond toward E413. Amoxapine and its metabolites were demonstrated as potent in vitro. Administration of low dosages of amoxapine with CPT-11 in mice achieved significant suppression of diarrhea and reduced tumor growth.

Conclusions: Amoxapine has great clinical potential to be rapidly translated to human subjects for irinotecan-induced diarrhea. Clin Cancer Res; 20(13); 3521–30. ©2014 AACR.
The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor
Authors: Swierczak Agnieszka , Cook Andrew D. , Lenzo Jason C. , Restall Christina M. , Doherty Judy P. , Anderson Robin L. , Hamilton John A.
Published: April 2014

Treatment options are limited for patients with breast cancer presenting with metastatic disease. Targeting of tumor-associated macrophages through the inhibition of colony-stimulating factor-1 receptor (CSF-1R), a key macrophage signaling pathway, has been reported to reduce tumor growth and metastasis, and these treatments are now in clinical trials. Here, we report that, surprisingly, treatment with neutralizing anti–CSF-1R and anti–CSF-1 antibodies, or with two different small-molecule inhibitors of CSF-1R, could actually increase spontaneous metastasis without altering primary tumor growth in mice bearing two independently derived mammary tumors. The blockade of CSF-1R or CSF-1 led to increased levels of serum G-CSF, increased frequency of neutrophils in the primary tumor and in the metastasis-associated lung, as well as increased numbers of neutrophils and Ly6Chi monocytes in the peripheral blood. Neutralizing antibody against the G-CSF receptor, which regulates neutrophil development and function, reduced the enhanced metastasis and neutrophil numbers that resulted from CSF-1R blockade. These results indicate that the role of the CSF-1R/CSF-1 system in breast cancer is far more complex than originally proposed, and requires further investigation as a therapeutic target. Cancer Immunol Res; 2(8); 765–76. ©2014 AACR.
Response to BRAF Inhibition in Melanoma Is Enhanced When Combined with Immune Checkpoint Blockade
Authors: Cooper Zachary A. , Juneja Vikram R. , Sage Peter T. , Frederick Dennie T. , Piris Adriano , Mitra Devarati , Lo Jennifer A. , Hodi F. Stephen , Freeman Gordon J. , Bosenberg Marcus W. , McMahon Martin , Flaherty Keith T. , Fisher David E. , Sharpe Arlene H. , Wargo Jennifer A.
Published: April 2014

BRAF-targeted therapy results in objective responses in the majority of patients; however, the responses are short lived (∼6 months). In contrast, treatment with immune checkpoint inhibitors results in a lower response rate, but the responses tend to be more durable. BRAF inhibition results in a more favorable tumor microenvironment in patients, with an increase in CD8+ T-cell infiltrate and a decrease in immunosuppressive cytokines. There is also increased expression of the immunomodulatory molecule PDL1, which may contribute to the resistance. On the basis of these findings, we hypothesized that BRAF-targeted therapy may synergize with the PD1 pathway blockade to enhance antitumor immunity. To test this hypothesis, we developed a BRAF(V600E)/Pten−/− syngeneic tumor graft immunocompetent mouse model in which BRAF inhibition leads to a significant increase in the intratumoral CD8+ T-cell density and cytokine production, similar to the effects of BRAF inhibition in patients. In this model, CD8+ T cells were found to play a critical role in the therapeutic effect of BRAF inhibition. Administration of anti-PD1 or anti-PDL1 together with a BRAF inhibitor led to an enhanced response, significantly prolonging survival and slowing tumor growth, as well as significantly increasing the number and activity of tumor-infiltrating lymphocytes. These results demonstrate synergy between combined BRAF-targeted therapy and immune checkpoint blockade. Although clinical trials combining these two strategies are ongoing, important questions still remain unanswered. Further studies using this new melanoma mouse model may provide therapeutic insights, including optimal timing and sequence of therapy. Cancer Immunol Res; 2(7); 643–54. ©2014 AACR.
Improving Cancer Patient Care with Combined Medication Error Reviews and Morbidity and Mortality Conferences
Authors: Ranchon Florence , You Benoît , Salles Gilles , Vantard Nicolas , Schwiertz Vérane , Gourc Chloé , Gauthier Noémie , Guédat Marie-Gabrielle , Souquet Pierre-Jean , Freyer Gilles , Trillet-Lenoir Véronique , Rioufol Catherine
Published: April 2014

Background: To reduce the occurrence of medication errors, a systemic approach was developed combining anti-neoplastic medication error reviews and morbidity and mortality conferences (M&MCs). We report the first experience of implementing this strategy in oncology. Methods: The case reports submitted to combined reviews were prepared by physicians and pharmacists, and medication error(s) were described and chronological and root-cause analyses were performed. Results: Ten combined reviews were conducted, which involved the departments of haematology, medical oncology, pneumology, gastroenterology and clinical oncology pharmacy. A total of 91 errors were analysed, of which 3 had reached the patient. Thirty-four corrective actions were proposed; 53% consisted of changes in practice, 35% in procedural reminders and 12% in on-ward education sessions. Conclusions: The combination of medication error reviews and M&MCs appears to be an efficient means of improving cancer patient safety and personnel proficiency. This multidisciplinary work is indispensable to improve future patient management through the critical analysis of past medical errors.
Severe Metabolic Acidosis in Adult Patients with Duchenne Muscular Dystrophy
Authors: Lo Cascio Christian M. , Latshang Tsogyal D. , Kohler Malcolm , Fehr Thomas , Bloch Konrad E.
Published: April 2014

Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential.
The Role of BMI1 as a Biomarker of Cancer Stem Cells in Head and Neck Cancer: A Review
Authors: Allegra Eugenia , Trapasso Serena , Pisani Davide , Puzzo Lidia
Published: April 2014

Emerging studies show that BMI1 (B cell-specific Moloney murine leukemia virus integration site 1) has an important function as a biomarker of cancer stem cells (CSCs), i.e. cells with self-renewal characteristics, capable of tumor initiation, progression, invasion, metastasis, tumor recurrence and resistance to chemotherapy and radiotherapy. The failure of current anticancer therapies can be attributed to the relative ineffectiveness of drug and radiation treatments on CSCs, thereby preserving the full capacity of the cells to reproduce tumors. The development of new strategies is currently hindered by the lack of reliable markers for the identification of these CSCs. At present, they have been isolated from solid tumors at various locations using a variety of surface markers, including CD34, CD133, CD24, CD44, CD29 and CD31, in addition to the methods of isolation and cell culture via the Wnt, BMI1, Notch and Hedgehog pathways. The discovery of specific tumor targets for CSCs would constitute a big step in the research for the definitive therapy against cancer. More studies are being conducted that consider the role of CSCs in head and neck cancers with potential for an impact on clinical-surgical outcomes from the knowledge that is being gained. A promising intracellular marker of CSCs in head and neck cancer is the oncoprotein BMI1, with specific data about its prognostic value based on the specific location.
A Novel Missense NDP Mutation [p.(Cys93Arg)] with a Manifesting Carrier in an Austrian Family with Norrie Disease
Authors: Parzefall Thomas , Lucas Trevor , Ritter Markus , Ludwig Martin , Ramsebner Reinhard , Frohne Alexandra , Schöfer Christian , Hengstschläger Markus , Frei Klemens
Published: April 2014

Norrie disease is a rare, X-linked genetic syndrome characterized by combined congenital blindness and progressive hearing impairment. Norrie disease is caused by alterations in the NDP gene encoding the growth factor norrin that plays a key role in vascular development and stabilization of the eye, inner ear and brain. We identified a family with 3 affected deafblind males and a single female carrier presenting with a serous retinal detachment but normal hearing. Genetic analysis revealed a novel c.277T>C missense mutation causing the substitution of a hydrophobic cysteine to a hydrophilic arginine [p.(Cys93Arg)] within the highly conserved cysteine knot domain of the norrin protein. These results should expand the scope for amniocentesis and genetic testing for Norrie disease which is gaining in importance due to novel postnatal therapeutic concepts to alleviate the devastating retinal symptoms of Norrie disease.
Off-Loading of Cyclic Hydrostatic Pressure Promotes Production of Extracellular Matrix by Chondrocytes
Authors: Tatsumura Masaki , Sakane Masataka , Ochiai Naoyuki , Mizuno Shuichi
Published: April 2014

The addition of cyclic hydrostatic pressure (cHP) to cell culture medium has been used to promote extracellular matrix (ECM) production by articular chondrocytes. Though a combination of cHP followed by atmospheric pressure (AP) has been examined previously, the rationale of such a combination was unclear. We compared the effects of loading once versus twice (combinations of cHP followed by AP) regarding both gene expression and biochemical and histological phenotypes of chondrocytes. Isolated bovine articular chondrocytes were embedded in a collagen gel and incubated for 14 days under conditions combining cHP and AP. The gene expression of aggrecan core protein and collagen type II were upregulated in response to cHP, and those levels were maintained for at least 4 days after cHP treatment. Accumulation of cartilage-specific sulfated glycosaminoglycans following cHP for 7 days and subsequent AP for 7 days was significantly greater than that of the AP control (p < 0.05). Therefore, incubation at AP after loading with cHP was found to beneficially affect ECM accumulation. Manipulating algorithms of cHP combined with AP will be useful in producing autologous chondrocyte-based cell constructs for implantation.
Preconditioning with Glutamine Protects against Ischemia/Reperfusion-Induced Hepatic Injury in Rats with Obstructive Jaundice
Authors: Xu Feng , Dai Chao-Liu , Peng Song-Lin , Zhao Yang , Jia Chang-Jun , Xu Yong-Qing
Published: April 2014

Objective: To ascertain whether glutamine (Gln) pretreatment protects rats with obstructive jaundice from hepatic ischemia/reperfusion (I/R) injury and to determine the underlying molecular mechanisms. Methods: An obstructive jaundice rat model was developed by bile duct ligation. On the first day after the operation, all rats were randomized into two groups and received oral Gln or normal saline (NS) daily for 7 days. Then both groups underwent a 15-min liver ischemia via the Pringle maneuver. Blood samples as well as liver and intestinal tissues were harvested and measured after 1, 6 and 24 h of reperfusion. Results: The results showed that the histological morphology of the liver and intestinal tissues significantly improved in the Gln group after I/R injury compared with the NS group. Serum proteins and enzymes associated with hepatic function also significantly improved in the Gln group. The level of glutathione increased and the levels of malondialdehyde and myeloperoxidase decreased in the Gln group. The levels of interleukin-1β and tumor necrosis factor-α decreased in the Gln group. Moreover, bcl-2 protein expression was upregulated and intercellular adhesion molecule 1 and bax protein expression downregulated in the Gln group; the caspase 3 mRNA level significantly increased in the Gln group. Conclusions: The study demonstrates that preconditioning with Gln significantly improves hepatic structure and function after I/R injury in rats with obstructive jaundice. The protective effect of Gln was mediated by the inhibition of reactive oxygen species and inflammation as well as a reduction in hepatocyte apoptosis.
Human Gingiva-Derived Mesenchymal Stromal Cells Contribute to Periodontal Regeneration in Beagle Dogs
Authors: Yu Xinbo , Ge Shaohua , Chen Shulan , Xu Quanchen , Zhang Jin , Guo Hongmei , Yang Pishan
Published: April 2014

Gingiva-derived mesenchymal stromal cells (GMSCs) have been considered as a promising alternative strategy for periodontal regeneration based on their potential for multilineage differentiation in vitro and the ability to form new bone in vivo. In order to investigate the capacity of GMSCs for periodontal regeneration and the fate of GMSCs during periodontal tissue repair, enhanced green fluorescent protein-labeled GMSCs were transplanted into class III furcation defects created in beagle dogs. The results showed that the transplanted GMSCs significantly enhanced the regeneration of the damaged periodontal tissue, including the alveolar bone, cementum and functional periodontal ligament (PDL). Moreover, GMSCs were able to differentiate into osteoblasts, cementoblasts and PDL fibroblasts in vivo. These findings indicate that GMSCs represent a novel cell source for periodontal tissue reconstruction.
Histological Changes in the Retina Provoked by Lithium Treatment in a Nocturnal Rodent (Lagostomus maximus maximus)
Authors: Calderón Claudia , Filippa Verónica , Fogal Teresa , Piezzi Ramón , Pelzer Lilian , Mohamed Fabian
Published: April 2014

Daily morphological variations have been previously described in the viscacha (Lagostomus maximus maximus) retina. The aim of this work was to determine the effects of lithium administration on the histology of retinas from this nocturnal rodent since lithium is a drug that has been shown to affect different parameters of circadian rhythms. Adult male viscachas were divided into 2 groups, injected daily with lithium chloride or vehicle for 35 days, and sacrificed at 08:00, 16:00, and 24:00 h for light and electron microscopy studies. The following morphometric parameters were analyzed: the thickness of the photoreceptor layer, the rod outer and inner segments, and the outer nuclear layer. The control group displayed a true daily cycle of photoreceptor renewal similar to that previously reported by us for (untreated) viscachas in their normal habitat. In all lithium-treated groups, we did not observe histological changes in the thickness measurement of the retinal layers. In these groups, the retinas presented ultrastructural characteristics similar to those observed in control animals sacrificed at 24:00 h. In conclusion, chronic lithium administration abolished the daily histological rhythm in the viscacha retina, probably via inhibition of the phagocytosis process in pigment epithelial cells.
Sustained Activation of Interferon Regulatory Factor 3 during Infection by Paramyxoviruses Requires MDA5
Authors: Grandvaux Nathalie , Guan Xiaochun , Yoboua Fabrice , Zucchini Nicolas , Fink Karin , Doyon Priscilla , Martin Lydie , Servant Marc J. , Chartier Stéfany
Published: April 2014

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are the main cytosolic sensors of single-stranded RNA viruses, including paramyxoviruses, and are required to initiate a quick and robust innate antiviral response. Despite different ligand-binding properties, the consensus view is that RIG-I and MDA5 trigger common signal(s) to activate interferon regulatory factor 3 (IRF-3) and NF-κB, and downstream antiviral and proinflammatory cytokine expression. Here, we performed a thorough analysis of the temporal involvement of RIG-I and MDA5 in the regulation of IRF-3 during respiratory syncytial virus (RSV) infection. Based on specific RNA interference-mediated knockdown of RIG-I and MDA5 in A549 cells, we confirmed that RIG-I is critical for the initiation of IRF-3 phosphorylation, dimerization and downstream gene expression. On the other hand, our experiments yielded the first evidence that knockdown of MDA5 leads to early ubiquitination and proteasomal degradation of active IRF-3. Conversely, ectopic expression of MDA5 prolonged RIG-I-induced IRF-3 activation. Altogether, we provide novel mechanistic insight into the temporal involvement of RIG-I and MDA5 in the innate antiviral response. While RIG-I is essential for initial IRF-3 activation, engagement of induced MDA5 is essential to prevent early degradation of IRF-3, thereby sustaining IRF-3-dependent antiviral gene expression. MDA5 plays a similar role during Sendai virus infection suggesting that this model is not restricted to RSV amongst paramyxoviruses.
A Plant-Derived Wound Therapeutic for Cost-Effective Treatment of Post-Surgical Scalp Wounds with Exposed Bone
Authors: Läuchli Severin , Vannotti Stefanie , Hafner Jürg , Hunziker Thomas , French Lars
Published: April 2014

Background: To evaluate efficacy and cost-effectiveness of a plant-derived wound dressing (ONE), a mixture of hypericum oil (Hypericum perforatum L.) and neem oil (Azadirachta indica A. Juss.), in scalp wounds with exposed bone. Patients and Methods: All patients with scalp wounds with exposed bone, following the excision of skin tumors, and treated with ONE in 2011 were included. Time of healing, wound size, area of exposed bone, ease of handling, pain, and complications were evaluated. Costs of dressings and nursing time were compared with those cited in literature for other treatment modalities. Results: Fifteen consecutive patients with a mean age of 76.87 ± 10.3 years (59-90 years) were analyzed. The mean wound size was 10.9 ± 6.84 cm2 (0.4-22.6 cm2) with 4.8 ± 5.9 cm2 (0.3-20.7 cm2) of exposed bone. The time of complete healing by secondary intention was 8.1 (4-20) weeks. Rapid formation of granulation tissue was observed which after 4 weeks covered the entire exposed bone surface in 11 of 15 cases (73%). Dressing change was simple with no pain reported; no infections or other complications occurred. Using ONE for a mean healing time of 56.7 days resulted in mean costs of EUR 423.73, which is substantially lower than those published for fascia lata, negative pressure therapy, or collagen matrix followed by skin grafting (EUR 1,612.82, EUR 4,411.80 and EUR 1,503.72, respectively). Conclusion: This retrospective, non-controlled analysis supports ONE as a simple-to-use and safe treatment option for scalp wounds with exposed bone. Treatment costs compare favorably to those published for other treatment modalities.
Suburothelial Interstitial Cells
Authors: Rusu Mugurel Constantin , Folescu Roxana , Mănoiu Vasile Sorin , Didilescu Andreea Cristiana
Published: April 2014

The suburothelium has received renewed interest because of its role in sensing bladder fullness. Various studies evaluated suburothelial myofibroblasts (MFs), interstitial cells (ICs), interstitial Cajal cells (ICCs) or telocytes (TCs), which resulted in inconsistencies in terminology and difficulties in understanding the suburothelial structure. In order to elucidate these issues, the use of electron microscopy seems to be an ideal choice. It was hypothesized that the cell population of the suburothelial band is heterogeneous in an attempt to clarify the above-mentioned inconsistencies. The suburothelial ICs of the bladder were evaluated by immunohistochemistry (IHC) and transmission electron microscopy (TEM). Bladder samples from 6 Wistar rats were used for IHC and TEM studies and human bladder autopsy samples were used for IHC. Desmin labeled only the detrusor muscle, while all the myoid structures of the bladder wall were positive for α-smooth muscle actin (SMA). A distinctive α-SMA-positive suburothelial layer was identified. A layered structure of the immediate suburothelial band was detected using TEM: (1) the inner suburothelial layer consisted of fibroblasts equipped for matrix synthesis; (2) the middle suburothelial layer consisted of smooth muscle cells (SMCs) and myoid ICCs, and (3) the outer suburothelial layer consisted of ICs with TC morphology, building a distinctive network. In conclusion, the suburothelial layer consists of distinctive types of ICs but not MFs. The myoid layer, with SMCs and ICCs, which could be considered identical to the α-SMA-positive cells in the suburothelial band, seems the best-equipped layer for pacemaking and signaling. Noteworthy, the network of ICs also seems suitable for stromal signaling.
Stress-Relieving Effects of Short-Term Balneotherapy - a Randomized Controlled Pilot Study in Healthy Adults
Authors: Matzer Franziska , Nagele Eva , Bahadori Babak , Dam Karl , Fazekas Christian
Published: April 2014

Background: Stress-relieving effects of balneotherapy compared to progressive muscle relaxation (PMR) and to resting were investigated by measuring subjective relaxation and salivary cortisol. It was also examined whether participants with a high versus low stress level would have a different relaxation response. Methods: A sample of healthy volunteers was randomized to balneotherapy, PMR, or a resting control group, each intervention lasting for 25 min. Pre- and post-intervention salivary cortisol samples were collected, and participants rated their status of relaxation on a quantitative scale. In addition, 3 questionnaires were applied to detect participants' stress level and bodily complaints. Results: 49 healthy participants were recruited (65.3% female). In a pre-post comparison, salivary cortisol decreased (F = 23.53, p < 0.001) and subjective relaxation ratings increased (F = 132.18, p < 0.001) in all 3 groups. Study participants in the balneotherapy group rated themselves as more relaxed after the intervention as compared to the other groups (F = 5.22, p < 0.009). Participants with a high versus low stress level differed in somatic symptoms and in morning cortisol levels, but showed a similar relaxation response. Conclusion: Findings suggest that compared to PMR and resting, balneotherapy seems to be more beneficial with regard to subjective relaxation effects and similarly beneficial with regard to a decrease in salivary cortisol.
An Earplug Technique to Reduce the Gag Reflex during Dental Procedures
Authors: Cakmak Yusuf Ozgur , Ozdogmus Ömer , Günay Yumusan , Gürbüzer Bahadır , Tezulaş Emre , Kaspar Elif Ciğdem , Hacıoglu Hüsniye
Published: April 2014

Background: The gag reflex is a frequent problem occurring during dental treatment procedures, especially while making impressions of the maxillary teeth. The present study aims to evaluate the efficacy of a simple earplug as an external auditory canal stimulator to supress the profound gag reflex and as a second step, to map areas of the oropharynx suppressed by this technique. Methods: In the first step of the study, 90 patients who had a gag reflex during the impression procedure were allocated to a study group, a sham group, and a control group for evaluating the efficacy of the earplug technique. Second, 20 new patients with a gag reflex were included in order to map the oropharnygeal areas suppressed by this technique. Results: The severity of the gag reflex was reduced in the earplug group (but not in the sham or the control group). The affected area included the hard palate, uvula, and the tongue but not the posterior wall of oropharynx. Conclusion: An earplug technique can be a useful, practical, and effective tool to overcome the gag reflex during oral procedures, such as impression procedures of maxillary teeth.
Can Nephrologists Use Ultrasound to Evaluate the Inferior Vena Cava A Cross-Sectional Study of the Agreement between a Nephrologist and a Cardiologist
Authors: Muniz Pazeli José , Fagundes Vidigal Daniel , Cestari Grossi Tarcísio , Silva Fernandes Natália Maria , Colugnati Fernando , Baumgratz de Paula Rogério , Sanders-Pinheiro Hélady
Published: April 2014

Background/Aims: The costs and the need for a specialist impair the implementation of ultrasonography for evaluating the inferior vena cava (IVC) to assess the volemic status in hemodialysis patients. We investigated whether a nephrologist with limited ultrasound training can accurately assess the IVC in patients undergoing hemodialysis. Methods: A cardiologist and a nephrologist consecutively measured the indexed IVC expiratory diameter (VCDi) and the IVC collapsibility index (IVCCI) of 52 patients during hemodialysis sessions. In protocol I, the nephrologist used a regular ultrasound system (RUS) and the cardiologist used a cardiovascular ultrasound equipment; in protocol II, the machines were interchanged. Pearson and kappa coefficients and the interexaminer agreement by the Bland-Altman method were calculated. Results: The VCDi measurements showed a strong correlation in both protocols (r = 0.88 and 0.84 in protocols I and II, respectively). The volemic classifications were excellent in protocol I (kappa = 0.82 and 0.93 by VCDi and IVCCI, respectively) and substantial in protocol II (kappa = 0.77 and 0.75 by VCDi and IVCCI, respectively). The interexaminer agreement on the VCDi measurements was very good in both protocols. Conclusions: Ultrasound evaluation of the IVC can be performed by nephrologists using an RUS to assess the volemic status in hemodialysis patients.