bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Basis of the Unfolded Protein Response
Authors: Korennykh Alexei , Walter Peter
Published: October 2012

The unfolded protein response (UPR) is a network of intracellular signaling pathways that maintain the protein-folding capacity of the endoplasmic reticulum (ER) in eukaryotic cells. Dedicated molecular sensors embedded in the ER membrane detect incompletely folded or unfolded proteins in the ER lumen and activate a transcriptional program that increases the abundance of the ER according to need. In metazoans the UPR additionally regulates translation and thus relieves unfolded protein load by globally reducing protein synthesis. If homeostasis in the ER cannot be reestablished, the metazoan UPR switches from the prosurvival to the apoptotic mode. The UPR involves a complex, coordinated action of many genes that is controlled by one ER-embedded sensor, Ire1, in yeasts, and three sensors, Ire1, PERK, and ATF6, in higher eukaryotes, including human. We discuss the emerging molecular understanding of the UPR and focus on the structural biology of Ire1 and PERK, the two recently crystallized UPR sensors.
Interaction between bradykinin and natriuretic peptides via RGS protein activation in HEK-293 cells
Authors: Dobrivojević Marina , Sinđić Aleksandra , Edemir Bayram , Kalweit Stefanie , Forssmann Wolf-Georg , Hirsch Jochen R.
Published: October 2012

In this study, the interaction of natriuretic peptides (NP) and bradykinin (BK) signaling pathways was identified by measuring membrane potential ( Vm) and intracellular Ca2+ using the patch-clamp technique and flow cytometry in HEK-293 cells. BK and NP receptor mRNA was identified using RT-PCR. BK (100 nM) depolarized cells activating bradykinin receptor type 2 (B2R) and Ca2+-dependent Cl− channels inhibitable by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB; 10 μM). The BK-induced Ca2+ signal was blocked by the B2R inhibitor HOE 140. [Des-Arg9]-bradykinin, an activator of B1R, had no effect on intracellular Ca2+. NP [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and urodilatin] depolarized HEK-293 cells inhibiting K+ channels. ANP, urodilatin, BNP [binding to natriuretic peptide receptor (NPR)-A] and 8-bromo-(8-Br)-cGMP inhibited the BK-induced depolarization while CNP (binding to NPR-Bi) failed to do so. The inhibitory effect on BK-triggered depolarization could be reversed by blocking PKG using the specific inhibitor KT 5823. BK-stimulated depolarization as well as Ca2+ signaling was completely blocked by the phospholipase C (PLC) inhibitor U-73122 (10 nM). The inositol 1,4,5-trisphosphate receptor blocker 2-aminoethoxydiphenyl borate (2-APB; 50 μM) completely inhibited the BK-induced Ca2+ signaling. UTP, another activator of the PLC-mediated Ca2+ signaling pathway, was blocked by U-73122 as well but not by 8-Br-cGMP, indicating an intermediate regulatory step for NP via PKG in BK signaling such as regulators of G-protein signaling (RGS) proteins. When RGS proteins were inhibited by CCG-63802 in the presence of BK and 8-Br-cGMP, cells started to depolarize again. In conclusion, as natural antagonists of the B2R signaling pathway, NP may also positively interact in pathological conditions caused by BK.
Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton
Authors: Ly Donald L. , Waheed Faiza , Lodyga Monika , Speight Pam , Masszi András , Nakano Hiroyasu , Hersom Maria , Pedersen Stine F. , Szászi Katalin , Kapus András
Published: October 2012

Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF translocation, since siRNA-mediated GEF-H1 downregulation suppresses these responses. While the osmotically induced RhoA activation promotes nuclear MRTF accumulation, the concomitant activation of p38 MAP kinase mitigates this effect. Moderate hyperosmotic stress (600 mosM) drives MRTF-dependent transcription through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell death takes precedence over epithelial-myofibroblast transition, a potential consequence of MRTF-mediated phenotypic reprogramming.
Trial-to-trial dynamics and learning in a generalized, redundant reaching task
Authors: Dingwell Jonathan B. , Smallwood Rachel F. , Cusumano Joseph P.
Published: October 2012

If humans exploit task redundancies as a general strategy, they should do so even if the redundancy is decoupled from the physical implementation of the task itself. Here, we derived a family of goal functions that explicitly defined infinite possible redundancies between distance ( D) and time ( T) for unidirectional reaching. All [ T, D] combinations satisfying any specific goal function defined a goal-equivalent manifold (GEM). We tested how humans learned two such functions, D/T = c (constant speed) and D·T = c, that were very different but could both be achieved by neurophysiologically and biomechanically similar reaching movements. Subjects were never explicitly shown either relationship, but only instructed to minimize their errors. Subjects exhibited significant learning and consolidation of learning for both tasks. Initial error magnitudes were higher, but learning rates were faster, for the D· T task than for the D/ T task. Learning the D/ T task first facilitated subsequent learning of the D· T task. Conversely, learning the D· T task first interfered with subsequent learning of the D/ T task. Analyses of trial-to-trial dynamics demonstrated that subjects actively corrected deviations perpendicular to each GEM faster than deviations along each GEM to the same degree for both tasks, despite exhibiting significantly greater variance ratios for the D/ T task. Variance measures alone failed to capture critical features of trial-to-trial control. Humans actively exploited these abstract task redundancies, even though they did not have to. They did not use readily available alternative strategies that could have achieved the same performance.
An Augmented Lagrangian Algorithm for Solving SemiinfiniteProgramming
Authors: Liu Qian , Wang Changyu
Published: October 2012

We present a smooth augmented Lagrangian algorithm for semiinfinite programming (SIP). For this algorithm, we establish a perturbation theorem under mild conditions. As a corollary of the perturbation theorem, we obtain the global convergence result, that is, any accumulation point of the sequence generated by the algorithm is the solution of SIP. We get this global convergence result without any boundedness condition or coercive condition. Another corollary of the perturbation theorem shows that the perturbation function at zero point is lower semi‐continuous if and only if the algorithm forces the sequence of objective function convergence to the optimal value of SIP. Finally, numerical results are given.
Recent Advances in the Deposition of Diamond Coatings on Co-Cemented Tungsten Carbides
Authors: Polini R. , Barletta M. , Rubino G. , Vesco S.
Published: October 2012

Co-cemented tungsten carbides, namely, hard metals are largely used to manufacture high wear resistant components in several manufacturing segments. Coating hard metals with superhard materials like diamond is of utmost interest as it can further extend their useful lifespan. The deposition of diamond coatings onto WC-Co can be extremely complicated as a result of poor adhesion. This can be essentially ascribed to (i) the mismatch in thermal expansion coefficients between diamond and WC-Co, at the typical high temperatures inside the chemical vapour deposition (CVD) chamber, generates large residual stresses at the interface; (ii) the role of surface Co inside the WC-Co matrix during diamond CVD, which promotes carbon dissolution and diffusion. The present investigation reviews the techniques by which Co-cemented tungsten carbides can be treated to make them prone to receive diamond coatings by CVD. Further, it proposes interesting ecofriendly and sustainable alternatives to further improve the diamond deposition process as well as the overall performance of the coated hard metals.
Venous Small Bowel Infarction: Intraoperative Laser Doppler Flowmetry Discriminates Critical Blood Supply and Spares Bowel Length
Authors: Käser S. A. , Glauser P. M. , Maurer C. A.
Published: October 2012

Introduction. In mesenteric infarction due to arterial occlusion, laser Doppler flowmetry and spectrometry are known reliable noninvasive methods for measuring microvascular blood flow and oxygen utilisation.Case Presentation. As an innovation we used these methods in a patient with acute extensive mesenteric infarction due to venous occlusion, occurring after radical right hemicolectomy. Aiming to avoid short bowel syndrome, we spared additional 110 cm of small bowel, instead of leaving only 80 centimetres of clinically viable small bowel in situ. The pathological examination showed only 5 mm of vital mucosa to be left distal to the dissection margin. No further interventions were necessary.Conclusion. Laser doppler flowmetry and spectrometry are potentially powerful methods to assist the surgeon’s decision-making in critical venous mesenteric perfusion, thus having an important impact on clinical outcome.
Toward Intelligent Intrusion Prediction for Wireless Sensor Networks Using Three-Layer Brain-Like Learning
Authors: Wu Jun , Liu Song , Zhou Zhenyu , Zhan Ming
Published: October 2012

The intrusion prediction for wireless sensor networks (WSNs) is an unresolved problem. Hence, the current intrusion detection schemes cannot provide enough security for WSNs, which poses a number of security challenges in WSNs. In many mission-critical applications, such as battle field, even though the intrusion detection systems (IDSs) without prediction capability could detect the malicious activities afterwards, the damages to the WSNs have been generated and could hardly be restored. In addition, sensor nodes usually are resource constrained, which limits the direct adoption of expensive intrusion prediction algorithm. To address the above challenges, we propose an intelligent intrusion prediction scheme that is able to enforce accurate intrusion prediction. The proposed scheme exploits a novel three-layer brain-like hierarchical learning framework, tailors, and adapts it for WSNs with both performance and security requirements. The implementation system of the proposed scheme is designed based on agent technology. Moreover, an attack experiment is done for getting training and test data set. Experiment results show that the proposed scheme has several advantages in terms of efficiency of implementation and high prediction rate. To our best knowledge, this paper is the first to realize intrusion prediction for WSNs.
Application-Oriented Fault Detection and Recovery Algorithm for Wireless Sensor and Actor Networks
Authors: Du Jinglin , Xie Li , Sun Xiaoyan , Zheng Ruoqin
Published: October 2012

Recent years have witnessed a growing interest in applications of wireless sensor and actor networks (WSANs). In WSANs, maintaining interactor connectivity is of vital concern in order to reach application level. Failure of a critical actor may partition the inter-actor network into disjoint segments. This paper proposed an application-oriented fault detection and recovery algorithm (AFDR), a novel distributed algorithm to reestablish connectivity. AFDR identifies critical actors and designates backups for them. A backup actor detects the critical node failure and initiates a recovery process via moving to the optimal position. The purpose of AFDR is to satisfy application requirements, reduce recovery overhead, and limit the impact of critical node failure on coverage and connectivity to the utmost. The effectiveness of AFDR is validated through simulation experiments.
The Immune Response and Its Therapeutic Modulation in Bronchiectasis
Authors: Daheshia Massoud , Prahl James D. , Carmichael Jacob J. , Parrish John S. , Seda Gilbert
Published: October 2012

Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interestingly, a defect in the immune system or suppression of immune response during conditions such as immunodeficiency may well predispose one to the devastating effects of BC. Thus, the outcome of an active immune response as detrimental or protective in the pathogenesis of BC may be dependent on the state of the patient's immunity, the severity of infection, and the magnitude of immune response. Here we reassess the function of the innate and acquired immunity in BC, the major sites of immune response, and the nature of the bioactive mediators. Furthermore, the potential link(s) between an ongoing immune response and structural alterations accompanying the disease and the success of therapies that can modulate the nature and extent of immune response in BC are elaborated upon.
Feasibility of Robotic-Assisted Laparoscopic Nephroureterectomy in Left Ventricular Assist Device Patient
Authors: Khemees Tariq A. , Shabsigh Ahmad
Published: October 2012

Left ventricular assist devices (LVADs) have revolutionized management options for patients with advanced heart failure. It is not uncommon for patients treated with these devices to present with noncardiac surgical conditions including urologic problems. Maintaining perioperative hemodynamic and hematologic stability is a special challenge. The minimally invasive surgery provides well-documented advantages over the open approach including a less operative blood loss and faster convalescence. In carefully selected patients, robotic-assisted surgery can be utilized in the management of patients with complex urologic diseases in a dire need for these benefits. We present the first case of robotic-assisted laparoscopic nephroureterectomy (RANU) with retroperitoneal lymph node dissection for upper tract transitional cell carcinoma (TCC) in a patient treated with LVAD.
Transcriptional Activity of PGC-1αand NT-PGC-1αIs Differentially Regulated by Twist-1 in Brown Fat Metabolism
Authors: Jun Hee-Jin , Gettys Thomas W. , Chang Ji Suk
Published: October 2012

Brown fat expresses two PGC-1αisoforms (PGC-1αand NT-PGC-1α) and both play a central role in the regulation of cellular energy metabolism and adaptive thermogenesis by interacting with a wide range of transcription factors including PPARγ, PPARα, ERRα, and NRF1. PGC-1αconsists of 797 amino acids, whereas alternative splicing of thePGC-1αgene produces a shorter protein called NT-PGC-1α(aa 1–270). We report in this paper that transcriptional activity of PGC-1αand NT-PGC-1αis differently affected by the transcriptional regulator, Twist-1. Twist-1 suppresses PGC-1αbut not NT-PGC-1α. The inhibition of PGC-1αactivity by Twist-1 is mediated by direct interaction through the C-terminal region of PGC-1α(aa 353–797). Thus, the absence of the corresponding C-terminal domain in NT-PGC-1αallows NT-PGC-1αto be free from Twist-1-mediated inhibition. Overexpression of Twist-1 in brown adipocytes suppresses transcription of a subset of PGC-1α-target genes involved in mitochondrial fatty acid oxidation and uncoupling (CPT1β, UCP1, and ERRα). In contrast, NT-PGC-1α-mediated induction of these genes is unaffected by Twist-1. These findings show that differences in inhibitory protein-protein interactions of PGC-1αand NT-PGC-1αwith Twist-1 lead to differential regulation of their function by Twist-1.
Ectopic Functioning Adrenocortical Oncocytic Adenoma (Oncocytoma) with Myelolipoma Causing Virilization
Authors: Surrey Lea F. , Thaker Ashesh A. , Zhang Paul J. , Karakousis Giorgos , Feldman Michael D.
Published: October 2012

Functioning adrenal adenomas are well-described entities that can rarely occur outside the adrenal gland in the ectopic adrenal tissue. Similarly, myelolipoma is an another benign lesion of the adrenal tissue which can rarely occur outside the adrenal gland. We report the first case of a testosterone producing an extra-adrenal adrenocortical oncocytoma accompanied by a myelolipoma. The patient presented with virilization and elevated androgen levels. Imaging revealed a retroperitoneal mass, which histologically consisted of oncocytes and intermingled myelolipoma. Postoperative androgen levels decreased to normal. The tumor cells were strongly positive for inhibin and Melan-A, supporting the adrenal origin. This case demonstrates a diagnostic challenge in which correlation with histology, immunohistochemistry, and serum endocrine studies led to the final diagnosis.
Microbiological Evaluation of the Effectiveness of Sewage Sludge Sanitization with Solar Drying Technology
Authors: Paluszak Zbigniew , Skowron Krzysztof , Sypuła Małgorzata , Skowron Karolina Jadwiga
Published: October 2012

The aim of study was to estimate the sanitization effectiveness of the sludge solar drying process carried out on technical scale in Poland based on the inactivation of bacteria and parasite eggs. Sewage sludge samples inoculated withEscherichia coli,SalmonellaSenftenberg W775and enterococci and perlon bags containingAscaris suumeggs were placed inside the carriers fixed in the dried sludge pile and on the shovels and frame of the sludge turner. The number of reisolated microorganisms was determined with MPN method and the percentage of invasiveA. suumeggs—with the microscope counting. On the basis of regression equations, the theoretical survivability and elimination rate of bacteria and parasite eggs were calculated. Experiment showed low hygienization efficiency of solar drying method. The theoretical survival time was 46–104 days in summer and 90–98 days in winter forS.Senftenberg W775and, respectively 42–55 and 71–148 days forE. coli, depending on the carriers location. Enterococci were able to survive for 52–168 days in summer and in winter its number increased. The decrease in the percentage of invasiveA. suumeggs was almost not observed. Results indicated that solar drying is a technology, which does not guarantee biosafety of product.
Staphylococcal Sepsis with Multiple Abscesses, Urinary Tract Infection, and Bilateral Renal Vein Thrombosis in a Patient with Uncontrolled Diabetes Mellitus
Authors: Khan Malik A. A. , Hunter Jonathan Michael , Tan Christopher , Seleem Mostafa , Stride Peter J. O.
Published: October 2012

We report a case of staphylococcal sepsis with vascular complications including peripheral emboli and renal vein thrombosis. Bilateral renal vein thrombosis has not been reported as a complication ofStaphylococcus aureus(SA) axillary abscess. Uncontrolled diabetes was the only detected predisposing medical condition. The patient was treated successfully with incision and drainage of soft-tissue abscesses and intravenous antibiotic for six weeks and with anticoagulation for renal vein thrombosis.
Acute Aortic Dissection Mimicking STEMI in the Catheterization Laboratory: Early Recognition Is Mandatory
Authors: Arrivi Alessio , Tanzilli Gaetano , Puddu Paolo Emilio , Truscelli Giovanni , Dominici Marcello , Mangieri Enrico
Published: October 2012

Coronary malperfusion due to type A aortic dissection is a life-threatening condition where timely recognition and treatment are mandatory. A 77-year-old woman underwent an acute evolving type A aortic dissection mimicking acute myocardial infarction. Two pathophysiologic mechanisms are discussed: either thrombosis migrating from a previously treated giant aneurism of proximal left anterior descending or a local arterial complication due to left main stenting. Recognition of these occurrences in the catheterization laboratory is important to look immediately for surgery.
A Best Possible Double Inequality for Power Mean
Authors: Li Yong-Min , Long Bo-Yong , Chu Yu-Ming
Published: October 2012

We answer the question: for any p, q ∈ ℝ with p ≠ q and p ≠ −q, what are the greatest value λ = λ(p, q) and the least value μ = μ(p, q), such that the double inequality holds for all a, b > 0 with a ≠ b? Where Mp(a, b) is the pth power mean of two positive numbers a and b.
Brain Connectivity Analysis: A Short Survey
Authors: Lang E. W. , Tomé A. M. , Keck I. R. , Górriz-Sáez J. M. , Puntonet C. G.
Published: October 2012

This short survey the reviews recent literature on brain connectivity studies. It encompasses all forms of static and dynamic connectivity whether anatomical, functional, or effective. The last decade has seen an ever increasing number of studies devoted to deduce functional or effective connectivity, mostly from functional neuroimaging experiments. Resting state conditions have become a dominant experimental paradigm, and a number of resting state networks, among them the prominent default mode network, have been identified. Graphical models represent a convenient vehicle to formalize experimental findings and to closely and quantitatively characterize the various networks identified. Underlying these abstract concepts are anatomical networks, the so-called connectome, which can be investigated by functional imaging techniques as well. Future studies have to bridge the gap between anatomical neuronal connections and related functional or effective connectivities.
Source Space Analysis of Event-Related Dynamic Reorganization of Brain Networks
Authors: Ioannides Andreas A. , Dimitriadis Stavros I. , Saridis George A. , Voultsidou Marotesa , Poghosyan Vahe , Liu Lichan , Laskaris Nikolaos A.
Published: October 2012

How the brain works is nowadays synonymous with how different parts of the brain work together and the derivation of mathematical descriptions for the functional connectivity patterns that can be objectively derived from data of different neuroimaging techniques. In most cases static networks are studied, often relying on resting state recordings. Here, we present a quantitative study of dynamic reconfiguration of connectivity for event-related experiments. Our motivation is the development of a methodology that can be used for personalized monitoring of brain activity. In line with this motivation, we use data with visual stimuli from a typical subject that participated in different experiments that were previously analyzed with traditional methods. The earlier studies identified well-defined changes in specific brain areas at specific latencies related to attention, properties of stimuli, and tasks demands. Using a recently introduced methodology, we track the event-related changes in network organization, at source space level, thus providing a more global and complete view of the stages of processing associated with the regional changes in activity. The results suggest the time evolving modularity as an additional brain code that is accessible with noninvasive means and hence available for personalized monitoring and clinical applications.
Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK
Authors: Wang Shao-Jun , Yang Hao-Yan , Xu Guo-Shuang
Published: October 2012

Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD) tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36) and Shangjuxu (ST37) in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.
The Role of HLA in Cord Blood Transplantation
Authors: Stavropoulos-Giokas Catherine , Dinou Amalia , Papassavas Andreas
Published: October 2012

In recent years, umbilical cord blood (CB), a rich source of hematopoietic stem cells (HSC), has been used successfully as an alternative HSC source to treat a variety of hematologic, immunologic, genetic, and oncologic disorders. CB has several advantages, including prompt availability of the transplant, decrease of graft versus host disease (GVHD) and better long-term immune recovery, resulting in a similar long-term survival. Studies have shown that some degree of HLA mismatches is acceptable. This review is intended to outline the main aspects of HLA matching in different settings (related, pediatric, adult, or double-unit HSCT), its effect on transplantation outcome and the role of HLA in donor selection.
Spin Waves Excitations of Co/Pt Multilayers
Authors: Zhou W.
Published: October 2012

The present work investigated interlayer couplings of [Co(20 Å)/Pt(30 Å)]5, [Co(4 Å)/Pt(7 Å)]30, and [Co(4 Å)/Pt(9 Å)]30 multilayers with strong perpendicular magnetic anisotropy (PMA). Brillouin light scattering measurements were utilized to obtain spin waves of these samples with in‐plane external magnetic fields. Interlayer couplings were found to be very sensitive to Pt thickness change from 7 Å to 9 Å, which implies that Pt atoms were more difficult to be polarized to provide interlayer coupling between Co layers than in the perpendicular external magnetic field situation. When Pt layer is 30 Å, the observed single spin wave can confirm the disappearance of interlayer coupling even when Co layer thickness is 20 Å.
Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages
Authors: Spentzas Thomas , Shappley Rebekah K. H. , Savorgnan Fabio , Meals Elizabeth , English B. Keith
Published: October 2012

Background. Methicillin-resistantStaphylococcus aureus(MRSA) can stimulate massive cytokine release. Ketamine suppresses tumor necrosis factor (TNF) secretion by MRSA-stimulated RAW264.7 macrophages, and the mechanism likely involves N-methyl-D-aspartic acid (NMDA) receptor antagonism. The downstream effects of NMDA-mediated TNF suppression, specifically the PI3K/Akt and mTOR modulation, have not been described.Methods. RAW264.7 cells were stimulated for 18 hrs with 105to 107 CFU/mL inocula of either of two prototypical community-acquired- (CA-) MRSA isolates, USA300 strain LAC and USA400 strain MW2. Then we added the NMDA inhibitors ketamine or 2R-amino-5-phosphonopentanoate (AP5), NMDA substrate, LY294002, and rapamycin in various combinations.Results. NMDA inhibition suppressed TNF secretion by almost a third compared to the no-ketamine control. When NMDA substrate was added, the TNF secretion increased by 10%. Addition of LY294002 suppressed TNF production by macrophages by 20%. Rapamycin exhibited a concentration-dependent TNF induction-suppression response: induction at doses of 0.1 and 1 ng/mL and suppression at 10 and 100 ng/mL. Induction of TNF was abolished when LY294002 was added and the suppression became uniform. Ketamine-induced suppression of TNF secretion was intensified 10–15% when rapamycin was added, but not when LY294002 was added.Conclusion. These findings suggest that NMDA-induced TNF suppression can be augmented by concurrent mTOR inhibition.
Effects of Heliox in Stable COPD Patients at Rest and during Exercise
Authors: Pecchiari Matteo
Published: October 2012

Heliox has been administered to stable chronic obstructive pulmonary disease (COPD) patients at rest and during exercise on the assumption that this low density mixture would have reduced work of breathing, dynamic hyperinflation, and, consequently, dyspnea sensation. Contrary to these expectations, beneficial effects of heliox in these patients at rest have been reported only sporadically, and the majority of the studies performed until now suggests that heliox is not a therapeutic option in spontaneously breathing resting COPD patients. On the other hand, when it is administered to COPD patients exercising at a constant work rate, heliox systematically decreases dyspnea sensation, and, often but not always, increases exercise tolerance. For these reasons, heliox has been evaluated as a non pharmacological tool to power rehabilitation programs. The conflicting results provided by the published trials probably point at a substantial heterogeneity of the COPD patients population in terms of respiratory mechanics and gas exchange. Therefore, further studies, aimed to the identification of mechanisms conditioning the response of exercising COPD patients to heliox, are warranted, before heliox administration, which is costly and cumbersome, can be routinely used in rehabilitation programs.
Salidroside Decreases Atherosclerotic Plaque Formation in Low-Density Lipoprotein Receptor-Deficient Mice
Authors: Zhang Bu-Chun , Li Wei-Ming , Guo Rong , Xu Ya-Wei
Published: October 2012

Salidroside is isolated fromRhodiola roseaand is one of the main active components inRhodiolaspecies. The present study was designed to evaluate the effects of Salidroside on atherosclerotic plaque formation in high-fat diet-(HFD-) fed female LDL receptor knockout (LDLr-/-) mice.LDLr-/-mice fed an atherogenic HFD for 12 weeks were divided into two groups. One group was administered Salidroside (50 mg/kg/oral gavage) daily for 8 weeks, while the control group was administered saline. Salidroside treatment reduced serum lipids levels and the plaque area through the arch to the abdominal aorta. Furthermore, Salidroside improved macrophage content and enhanced collagen and smooth muscle cells contents in the aortic sinus. These changes were associated with reduced MCP-1, VCAM-1, and VCAM-1 protein expression in atherosclerotic aortas. All these results suggest that Salidroside decreases atherosclerotic plaques formation via effects on lipid lowering and anti-inflammation in HFD-fed LDLr−/−mice.
Scalp Metastasis from Leiomyosarcoma of the Inferior Vena Cava Sign as the First Clinical Sign: A Case Report
Authors: Prieto Muñoz Isabel , Pardo Masferrer Jose
Published: October 2012

The presentation of scalp metastases from leiomyosarcoma of the vena cava is an extremely infrequent event. There are no other publications that describe such finding and very few of leiomyosarcoma in vessels. About this event we have reviewed the English literature describing studies on scalp metastases and skin metastases in general: their incidence, origin, clinical appearance, meaning, and diagnosis. The case we describe would be the second one presented worldwide because, as far as we know, it has been only one more published in 2005.
Adrenal Cortex-Sparing Surgery for Bilateral Multiple Pheochromocytomas in a Patient with Von Hippel-Lindau Disease
Authors: Esen Tarık , Acar Ömer , Tefekli Ahmet , Musaoğlu Ahmet , Rozanes İzzet , Emre Ali
Published: October 2012

Pheochromocytomas can be a part of familial neoplastic syndromes, in which case they tend to be multiple and involve both adrenal glands. Therefore, sparing adrenocortical function represents a major concern while dealing with these hereditary lesions. Herein, we describe the clinical characteristics and the management strategy of a patient with von Hippel-Lindau (VHL) disease who had multiple, bilateral pheochromocytomas as well as bilateral renal masses, pancreatic masses, and a paracaval mass. Only a portion of the left adrenal gland has remained in situ after two consecutive open surgeries and a percutaneous radiofrequency ablation which have been performed to treat the various components of this syndrome. No adrenal or extra-adrenal pheochromocytoma recurrences have been detected during a follow-up period of more than 2 years. Pancreatic and adrenal functions were normal throughout the postoperative period and never necessitated any replacement therapy. Adrenal cortex-sparing surgery is a valid option for VHL disease patients who present with synchronous bilateral adrenal pheochromocytomas.
Number of Patients per Cohort and Sample Size Considerations Using Dose Escalation with Overdose Control
Authors: Tighiouart Mourad , Rogatko André
Published: October 2012

The main objective of cancer phase I clinical trials is to determine a maximum tolerated dose (MTD) of a new experimental treatment. In practice, most of these trials are designed so that three patients per cohort are treated at the same dose level. In this paper, we compare the safety and efficiency of trials using the escalation with overdose control (EWOC) scheme designed with three or only one patient per cohort. We show through simulations that the number of patients per cohort does not impact the proportion of patients given therapeutic doses, safety of the trial, and efficiency of the estimate of the MTD. Additionally, we present guidelines and tabulated values on the number of patients needed to design a phase I cancer clinical trial using EWOC to achieve a given accuracy of the estimate of the MTD.
Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine
Authors: Rennie Kerry , Gruslin Andrée , Hengstschläger Markus , Pei Duanqing , Cai Jinglei , Nikaido Toshio , Bani-Yaghoub Mahmud
Published: October 2012

The amniotic membrane (AM) and amniotic fluid (AF) have a long history of use in surgical and prenatal diagnostic applications, respectively. In addition, the discovery of cell populations in AM and AF which are widely accessible, nontumorigenic and capable of differentiating into a variety of cell types has stimulated a flurry of research aimed at characterizing the cells and evaluating their potential utility in regenerative medicine. While a major focus of research has been the use of amniotic membrane and fluid in tissue engineering and cell replacement, AM- and AF-derived cells may also have capabilities in protecting and stimulating the repair of injured tissues via paracrine actions, and acting as vectors for biodelivery of exogenous factors to treat injury and diseases. Much progress has been made since the discovery of AM and AF cells with stem cell characteristics nearly a decade ago, but there remain a number of problematic issues stemming from the inherent heterogeneity of these cells as well as inconsistencies in isolation and culturing methods which must be addressed to advance the field towards the development of cell-based therapies. Here, we provide an overview of the recent progress and future perspectives in the use of AM- and AF-derived cells for therapeutic applications.
Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration
Authors: Weber Catherine , Kasberg Heather , Copelan Edward
Published: October 2012

Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.
Crossed Renal Ectopia without Fusion—An Unusual Cause of Acute Abdominal Pain: A Case Report
Authors: Ramaema D. P. , Moloantoa W. , Parag Y.
Published: October 2012

Introduction. Crossed renal ectopia is a congenital anomaly which usually goes unnoticed as most cases are asymptomatic. The majority, 90% of these are fused.Case Presentation. We report an unusual presentation of a case of crossed renal ectopia without fusion. Our patient is a 16-year-old adolescent male, previously fit and healthy, who presented with acute onset of abdominal pain. The clinical suspicion was that of an abdominal aortic aneurysm. Computed tomography with intravenous contrast revealed nonfused crossed renal ectopia.Conclusion. Although renal ectopia is an uncommon cause of acute abdominal pain, there should be an index of clinical suspicion in previously healthy individuals presenting with acute abdominal pain.
Prescription Patterns of Chinese Herbal Products for Osteoporosis in Taiwan: A Population-Based Study
Authors: Shih Wei-Tai , Yang Yao-Hsu , Chen Pau-Chung
Published: October 2012

Background. Traditional Chinese medicine (TCM) includes Chinese herbal products (CHPs), acupuncture, and traumatology manipulative therapies. TCM physicians often prescribe CHP to treat patients with osteoporosis; however, the drugs used and their patterns of prescriptions have yet to be characterized. This study, therefore, aimed to evaluate the CHP used for the treatment of osteoporosis in Taiwan and their prescription patterns.Methods. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was analyzed to evaluate the frequencies and percentages of herbal formula and single herb prescriptions for osteoporosis. Association rules were then applied to evaluate the CHP coprescription patterns and the prevalence of osteoporosis.Results. The osteoporosis cohort included 16 544 patients, of whom more than 70% had used TCM on one or more occasion. Of these patients, 4 292 (25.9%) had been hospitalized at least once because of fracture. Du-Huo-Ji-Sheng-Tang and Du Zhong (Cortex Eucommiae) were the most frequently prescribed herbal formula and single herb, respectively, for the treatment of osteoporosis.Conclusion. This study identified patterns of CHP use for the treatment of osteoporosis. However, further research is required to fully elucidate the efficacy and safety of these CHP.
Spontaneous Resolution of Mirror Syndrome following Demise of Hydropic Twin
Authors: Oliver Kate E. , Hickey Kimberly W. , Petersen Scott M.
Published: October 2012

Maternal mirror syndrome is a rare consequence of fetal hydrops. By convention, delivery is recommended in pregnancies complicated by mirror syndrome due to grave fetal prognosis. We describe a case of a dichorionic, diamniotic twin gestation complicated by hydrops fetalis of twin B. The patient declined selective feticide. Two weeks later, intrauterine fetal demise of fetus B was diagnosed and complete resolution of mirror syndrome followed. Unaddressed, mirror syndrome can lead to significant maternal and fetal complications. This case illustrates resolution of mirror syndrome following spontaneous intrauterine demise of the hydropic fetus.
Consensus of the Present and Prospects on Endoscopic Diagnosis and Treatment in East Asian Countries
Authors: Kamiya Takeshi , Joh Takashi , Sollano Jose D. , Zhu Qi , Kachintorn Udom , Aziz Rani Abdul , Hahm Ki-Baik , Takahashi Shin'ichi , Kinoshita Yoshikazu , Matsumoto Takayuki , Naito Yuji , Takeuchi Koji , Arakawa Tetsuo , Terano Akira
Published: October 2012

Background and Aim. New diagnostic or therapeutic methods in endoscopy have been used. Current clinical application of these procedures is not well known. The aim of this study is to investigate the present situation on endoscopic diagnosis and treatment of gastrointestinal disorders in East Asian countries. Method. A representative member from the International Gastrointestinal Consensus Symposium Committee provided a questionnaire to physicians in China, Indonesia, Japan, Korea, the Philippines, and Thailand. Results. In total, 514 physicians including gastroenterologists, surgeons, and general practitioners enrolled. The most frequently occurring disorder as the origin of upper gastrointestinal bleeding is gastric ulcer. Capsule endoscopy is selected as the first choice for the diagnosis of small intestine bleeding. The second choice was double-balloon endoscopy or angiography. For patients with gastric adenoma, the number of physicians who choose endoscopic mucosal resection is larger than those selecting endoscopic submucosal dissection (ESD) in China, Indonesia, the Philippines, and Thailand. ESD is chosen first in Japan and Korea. Conclusion. New instruments or techniques on endoscopy have not come into wide use yet, and there is diversity in the situation on it in Asian countries. We should unify the endoscopic diagnostic criteria or treated strategy in patients with GI disease.
Global Stability Analysis of SEIR Model with Holling Type II Incidence Function
Authors: Safi Mohammad A. , Garba Salisu M.
Published: October 2012

A deterministic model for the transmission dynamics of a communicable disease is developed and rigorously analysed. The model, consisting of five mutually exclusive compartments representing the human dynamics, has a globally asymptotically stable disease-free equilibrium (DFE) whenever a certain epidemiological threshold, known as the basicreproduction number(ℛ0), is less than unity; in such a case the endemic equilibrium does not exist. On the other hand, when the reproduction number is greater than unity, it is shown, using nonlinear Lyapunov function of Goh-Volterra type, in conjunction with the LaSalle's invariance principle, that the unique endemic equilibrium of the model is globally asymptotically stable under certain conditions. Furthermore, the disease is shown to be uniformly persistent wheneverℛ0>1.
A Rare Chromosome 3 Imbalance and Its Clinical Implications
Authors: Sims Karen , Mazzaschi Roberto L. P. , Payne Emilie , Hayes Ian , Love Donald R. , George Alice M.
Published: October 2012

The duplication of chromosome 3q is a rare disorder with varying chromosomal breakpoints and consequently symptoms. Even rarer is the unbalanced outcome from a parental inv(3) resulting in duplicated 3q and a deletion of 3p. Molecular karyotyping should aid in precisely determining the length and breakpoints of the 3q+/3p− so as to better understand a child’s future development and needs. We report a case of an infant male with a 57.5 Mb duplication from 3q23-qter. This patient also has an accompanying 1.7 Mb deletion of 3p26.3. The duplicated segment in this patient encompasses the known critical region of 3q26.3-q27, which is implicated in the previously reported 3q dup syndrome; however, the accompanying 3p26.3 deletion is smaller than the previously reported cases. The clinical phenotype of this patient relates to previously reported cases of 3q+ that may suggest that the accompanying 1.7 Mb heterozygous deletion is not clinically relevant. Taken together, our data has refined the location and extent of the chromosome 3 imbalance, which will aid in better understanding the molecular underpinning of the 3q syndrome.
Electrooptic and Dielectric Studies in Cadmium Sulphide Nanorods/Ferroelectric Liquid Crystal Mixtures
Authors: Malik Praveen , Chaudhary Ashok , Mehra Rohit , Raina K. K.
Published: October 2012

We present the results based on the electrooptic and dielectric studies in cadmium sulphide (CdS) nanorods/ferroelectric liquid crystal mixtures. Doping of CdS nanorods increases the spontaneous polarization and response time, which due to large dipole-dipole interaction and increase in anchoring energies exists between nanorods and FLC molecules. Dielectric measurements revealed a decrease (~40% for 0.3% CdS in FLC) in permittivity and dielectric strength in doped sample cell than pure FLC mixture. A decrease in dc conductivity and relaxation frequency with doping concentration was also noticed. The preexponent factor and fractional exponent factor are found as predicated by existing theories.
Controversies and Recent Advances in Hematopoietic Cell Transplantation for Follicular Non-Hodgkin Lymphoma
Authors: Kanate Abraham S. , Kharfan-Dabaja Mohamed A. , Hamadani Mehdi
Published: October 2012

Commonly designated as an indolent non-Hodgkin lymphoma, follicular lymphoma (FL) presents with striking pathobiological and clinical heterogeneity. Initial management strategies for FL have evolved to involve combination chemoimmunotherapy and/or radio-immunoconjugates. Unfortunately even with the best available nontransplant treatment, which nowadays results in higher frequency of response, FL remains incurable. Although considered a feasible therapeutic option, the use of hematopoietic cell transplantation (HCT) remains controversial. The appropriate timing, graft source, and intensity of HCT conditioning regimens in FL are often matters of debate. Herein we review the available published data pertaining to the use of autologous or allogeneic HCT in patients with FL across different stages of the disease, discuss major recent advances in the field, and highlight avenues for future research. The current literature does not support a role of HCT for FL in first remission, but in the relapsed setting autologous HCT remains appropriate for patients with early chemosensitive relapses, while allogeneic transplantation remains the sole curative modality for this disease, in relatively younger patients without significant comorbidities.