bluuebunny/crossref_metadata_2025 huggingface dataset:
The unsilent majority–TRPV1 drives “spontaneous” transmission of unmyelinated primary afferents within cardiorespiratory NTS
Authors: Andresen Michael C. , Hofmann Mackenzie E. , Fawley Jessica A.
Published: October 2012

Cranial primary afferent sensory neurons figure importantly in homeostatic control of visceral organ systems. Of the two broad classes of visceral afferents, the role of unmyelinated or C-type class remains poorly understood. This review contrasts key aspects of peripheral discharge properties of C-fiber afferents and their glutamate transmission mechanisms within the solitary tract nucleus (NTS). During normal prevailing conditions, most information arrives at the NTS through myelinated A-type nerves. However, most of visceral afferent axons (75–90%) in NTS are unmyelinated, C-type axons. Centrally, C-type solitary tract (ST) afferent terminals have presynaptic transient receptor potential vanilloid type 1 (TRPV1) receptors. Capsaicin activation of TRPV1 blocks phasic or synchronous release of glutamate but facilitates release of glutamate from a separate pool of vesicles. This TRPV1-operated pool of vesicles is active at normal temperatures and is responsible for actively driving a 10-fold higher release of glutamate at TRPV1 compared with TRPV1− terminals even in the absence of afferent action potentials. This novel TRPV1 mechanism is responsible for an additional asynchronous release of glutamate that is not present in myelinated terminals. The NTS is rich with presynaptic G protein-coupled receptors, and the implications of TRPV1-operated glutamate offer unique targets for signaling in C-type sensory afferent terminals from neuropeptides, inflammatory mediators, lipid metabolites, cytokines, and cannabinoids. From a homeostatic view, this combination could have broad implications for integration in chronic pathological disturbances in which the numeric dominance of C-type endings and TRPV1 would broadly disturb multisystem control mechanisms.
The scavenger endothelial cell: a new player in homeostasis and immunity
Authors: Sørensen Karen Kristine , McCourt Peter , Berg Trond , Crossley Clive , Couteur David Le , Wake Kenjiro , Smedsrød Bård
Published: October 2012

To maintain homeostasis, the animal body is equipped with a powerful system to remove circulating waste.1This review presents evidence that the scavenger endothelial cell (SEC) is responsible for the clearance of blood-borne waste macromolecules in vertebrates. SECs express pattern-recognition endocytosis receptors (mannose and scavenger receptors), and in mammals, the endocytic Fc gamma-receptor IIb2. This cell type has an endocytic machinery capable of super-efficient uptake and degradation of physiological and foreign waste material, including all major classes of biological macromolecules. In terrestrial vertebrates, most SECs line the wall of the liver sinusoid. In phylogenetically older vertebrates, SECs reside instead in heart, kidney, or gills. SECs, thus, by virtue of their efficient nonphagocytic elimination of physiological and microbial substances, play a critical role in the innate immunity of vertebrates. In major invertebrate phyla, including insects, the same function is carried out by nephrocytes. The concept of a dual-cell principle of waste clearance is introduced to emphasize that professional phagocytes (macrophages in vertebrates; hemocytes in invertebrates) eliminate larger particles (>0.5 μm) by phagocytosis, whereas soluble macromolecules and smaller particles are eliminated efficiently and preferentially by clathrin-mediated endocytosis in nonphagocytic SECs in vertebrates or nephrocytes in invertebrates. Including these cells as important players in immunology and physiology provides an additional basis for understanding host defense and tissue homeostasis.
In vivo regulation of renal expression of (pro)renin receptor by a low-sodium diet
Authors: Matavelli Luis C. , Huang Jiqian , Siragy Helmy M.
Published: October 2012

Effects of low salt (LS) on (pro)renin receptor (PRR) expression are not well established. We hypothesized that LS enhances renal PRR expression via the cGMP-protein kinase G (PKG) signaling pathway. Sprague-Dawley rats were fed a normal-salt (NS) or LS diet associated with intrarenal cortical administration of vehicle (V), the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (l-NAME), the NO donor S-nitroso- N-acetyl-dl-penicillamine (SNAP), the cGMP analog 8-bromoguanosine (8-Br)-cGMP, the guanylyl cyclase inhibitor 1H-[1, 2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or a PKG inhibitor (PKGi) for 6 days via osmotic minipump. We evaluated the effects of each treatment on renal interstitial fluid (RIF) levels of nitrate/nitrite and cGMP and renal PRR expression. There were no significant changes in blood pressure with any of the treatments. Urinary sodium excretion was significantly lower in rats given a LS diet. Compared with NS + V, RIF nitrate/nitrite and cGMP levels increased in LS + V rats. In NS groups, RIF nitrate/nitrite and cGMP levels did not change with l-NAME, ODQ, or PKGi and increased in response to SNAP. 8-Br-cGMP increased RIF cGMP but not RIF nitrate/nitrite. In LS groups, RIF nitrate/nitrite decreased with l-NAME and did not change with ODQ or PKGi whereas RIF cGMP decreased with l-NAME, ODQ, and PKGi. PRR mRNA and protein increased in LS + V. In NS rats, PRR mRNA and protein increased in response to 8-Br-GMP and were not affected by any of other treatments. In LS rats, PRR mRNA and protein decreased significantly in response to l-NAME, ODQ, and PKGi. We conclude that LS intake enhances renal expression of PRR via cGMP-PKG signaling pathway.
Liver X receptor agonists decrease ENaC-mediated sodium transport in collecting duct cells
Authors: Soodvilai Sunhapas , Jia Zhanjun , Fongsupa Somsak , Chatsudthipong Varanuj , Yang Tianxin
Published: October 2012

Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol, fatty acid, and glucose metabolism in various tissues. However, the renal action of LXRs is not well understood. Here we investigated the effects of LXR-activating ligands on modulation of epithelial sodium channel (ENaC)-mediated sodium transport in collecting duct cells. Exposure of the M1 cells to the synthetic LXR agonists T0901317 and GW3965 or the natural ligand 22R-hydroxycholesterol for 24 h decreased amiloride-sensitive sodium transport, corresponding with an increase of transepithelial resistance. The inhibition of amiloride-sensitive sodium transport after incubation with T0901317 or GW3965 was not mediated by a reduction of Na+/K+-ATPase-mediated basolateral sodium transport. On the other hand, T0901317 and GW3965 decreased mRNA abundance and membrane expression of ENaC. Preincubation the monolayer with GW3965 attenuated aldosterone-induced stimulation sodium transport. In primary cultures of collecting duct cells, T0901317 and GW3965 similarly inhibited ENaC transport function as in M1 cells. This is the first evidence showing LXR-activating ligands modulate ENaC-mediated sodium transport in collecting duct cells. These results suggest that LXRs may represent a novel therapeutic target for treatment of conditions with dysregulation of ENaC such as hypertension.
Iodinated contrast media cause endothelial damage leading to vasoconstriction of human and rat vasa recta
Authors: Sendeski Mauricio M. , Persson Anja Bondke , Liu Zhi Zhao , Busch Jonas F. , Weikert Steffen , Persson Pontus B. , Hippenstiel Stefan , Patzak Andreas
Published: October 2012

Contrast-induced acute kidney injury is an important clinical event with a worldwide increasing number of cases. Medullary hypoperfusion and hypoxia due to constriction of vasa recta are main factors in the pathophysiology of acute kidney injury. However, the mechanism of contrast media (CM)-induced vessel constriction is not known. We tested the hypothesis that vasa recta constriction is a consequence of endothelial dysfunction due to the cytotoxicity of CM. Human and rat descending vasa recta (DVR) were isolated and perfused with CM, and the luminal diameter was analyzed. For morphological analysis of the endothelium, renal arteries were CM perfused and then processed for electron microscopy. Transcellular electrical resistance was used to estimate CM-induced changes in the permeability of human umbilical vein endothelial cell (HUVEC) layers. Perfusion with CM constricted human and rat DRV (to 54.3 and 50.9% of initial diameter, respectively). This was blunted by adrenomedullin (77.7 and 77.1%, respectively). The ANG II response was enhanced by CM in rat DVR (reduction to 15.6 and 35.0% of initial diameter, respectively). Adrenomedullin blunted this effect (67.5%). CM led to endothelial damage of renal arteries characterized by a ragged surface, with sharply protruding intimal folds, spindle-like shape, and bulging in the lumen. These phenomena were reduced by adrenomedullin. The permeability of HUVEC cell layers was increased by CM, and this went along with increased myosin light chain phosporylation. Again, adremonedullin reduced the CM effect. Our study suggests that the constrictor effect of CM on the renal medullary microvasculature is a consequence of endothelial cell damage and the resulting endothelial dysfunction.
Extracellular 2′,3′-cAMP-adenosine pathway in proximal tubular, thick ascending limb, and collecting duct epithelial cells
Authors: Jackson Edwin K. , Gillespie Delbert G.
Published: October 2012

In a previous study, we demonstrated that human proximal tubular epithelial cells obtained from a commercial source metabolized extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP and extracellular 2′-AMP and 3′-AMP to adenosine (the extracellular 2′,3′-cAMP-adenosine pathway; extracellular 2′,3′-cAMP → 2′-AMP + 3′-AMP → adenosine). The purpose of this study was to investigate the metabolism of extracellular 2′,3′-cAMP in proximal tubular vs. thick ascending limb vs. collecting duct epithelial cells freshly isolated from their corresponding nephron segments obtained from rat kidneys. In epithelial cells from all three nephron segments, 1) extracellular 2′,3′-cAMP was metabolized to 2′-AMP and 3′-AMP, with 2′-AMP > 3′-AMP, 2) the metabolism of extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP was not inhibited by either 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor) or 1,3-dipropyl-8-p-sulfophenylxanthine (ecto-phosphodiesterase inhibitor), 3) extracellular 2′,3′-cAMP increased extracellular adenosine levels, 4) 3′-AMP and 2′-AMP were metabolized to adenosine with an efficiency similar to that of 5′-AMP, and 5) the metabolism of 5′-AMP, 3′-AMP, and 2′-AMP was not inhibited by α,β-methylene-adenosine-5′-diphosphate (CD73 inhibitor). These results support the conclusion that renal epithelial cells all along the nephron can metabolize extracellular 2′,3′-cAMP to 2′-AMP and 3′-AMP and can efficiently metabolize extracellular 2′-AMP and 3′-AMP to adenosine and that the metabolic enzymes involved are not the classical phosphodiesterases nor ecto-5′-nucleotidase (CD73). Because 2′,3′-cAMP is released by injury and because previous studies demonstrate that the extracellular 2′,3′-cAMP-adenosine pathway stimulates epithelial cell proliferation via adenosine A2B receptors, the present results suggest that the extracellular 2′,3′-cAMP-adenosine pathway may help restore epithelial cells along the nephron following kidney injury.
Evidence for high-fidelity timing-dependent synaptic plasticity of human motor cortex
Authors: Cash R. F. H. , Mastaglia F. L. , Thickbroom G. W.
Published: October 2012

A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons [known as indirect (I)-waves] which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5 ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing-dependent plasticity models. Consequently, we hypothesized that if the second stimulus is delivered so as not to coincide with I-wave timing, it should lead to LTD. We performed a crossover study in 10 subjects in which TMS doublets were timed to coincide (1.5-ms IPI, ITMS1.5) or not coincide (2-ms IPI, ITMS2) with I-wave firing. Single pulse motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS1.5 corticomotor excitability was increased by ∼60% for 15 min ( P < 0.05) and returned to baseline by 20 min. Increasing the IPI by just 500 μs to 2 ms reversed the aftereffect, and MEP amplitude was significantly reduced (∼35%, P < 0.05) for 15 min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged, suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS2 did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal resolution of the order of a few hundreds of microseconds.
Electrical neuroimaging during auditory motion aftereffects reveals that auditory motion processing is motion sensitive but not direction selective
Authors: Magezi David A. , Buetler Karin A. , Chouiter Leila , Annoni Jean-Marie , Spierer Lucas
Published: October 2012

Following prolonged exposure to adaptor sounds moving in a single direction, participants may perceive stationary-probe sounds as moving in the opposite direction [direction-selective auditory motion aftereffect (aMAE)] and be less sensitive to motion of any probe sounds that are actually moving (motion-sensitive aMAE). The neural mechanisms of aMAEs, and notably whether they are due to adaptation of direction-selective motion detectors, as found in vision, is presently unknown and would provide critical insight into auditory motion processing. We measured human behavioral responses and auditory evoked potentials to probe sounds following four types of moving-adaptor sounds: leftward and rightward unidirectional, bidirectional, and stationary. Behavioral data replicated both direction-selective and motion-sensitive aMAEs. Electrical neuroimaging analyses of auditory evoked potentials to stationary probes revealed no significant difference in either global field power (GFP) or scalp topography between leftward and rightward conditions, suggesting that aMAEs are not based on adaptation of direction-selective motion detectors. By contrast, the bidirectional and stationary conditions differed significantly in the stationary-probe GFP at 200 ms poststimulus onset without concomitant topographic modulation, indicative of a difference in the response strength between statistically indistinguishable intracranial generators. The magnitude of this GFP difference was positively correlated with the magnitude of the motion-sensitive aMAE, supporting the functional relevance of the neurophysiological measures. Electrical source estimations revealed that the GFP difference followed from a modulation of activity in predominantly right hemisphere frontal-temporal-parietal brain regions previously implicated in auditory motion processing. Our collective results suggest that auditory motion processing relies on motion-sensitive, but, in contrast to vision, non-direction-selective mechanisms.
Synaptic activation of bulbospongiosus motoneurons via dorsal gray commissural inputs
Authors: Best Tyler K. , Marson Lesley , Thor Karl B. , Burgard Edward C.
Published: October 2012

Ejaculation is controlled by coordinated and rhythmic contractions of bulbospongiosus (BSM) and ischiocavernosus muscles. Motoneurons that innervate and control BSM contractions are located in the dorsomedial portion of the ventral horn in the L5–6 spinal cord termed the dorsomedial (DM) nucleus. We characterized intrinsic properties of DM motoneurons as well as synaptic inputs from the dorsal gray commissure (DGC). Electrical stimulation of DGC fibers elicited fast inhibitory and excitatory responses. In the presence of glutamate receptor antagonists, both fast GABAergic as well as glycinergic inhibitory postsynaptic potentials (IPSPs) were recorded. No slow GABAB-mediated inhibition was evident. In the presence of GABAA and glycine receptor antagonists, DGC stimulation elicited fast glutamatergic excitatory responses that were blocked by application of CNQX. Importantly, a slow depolarization (timescale of seconds) was routinely observed that sufficiently depolarized the DM motoneurons to fire “bursts” of action potentials. This slow depolarization was elicited by a range of stimulus train frequencies and was insensitive to glutamate receptor antagonists (CNQX and d-APV). The slow depolarization was accompanied by an increase in membrane resistance with an extrapolated reversal potential near the K+ Nernst potential. It was mediated by the combination of the block of a depolarization-activated K+ current and the activation of a QX-314-sensitive cation current. These results demonstrate that fast synaptic responses in DM motoneurons are mediated primarily by glutamate, GABA, and glycine receptors. In addition, slow nonglutamatergic excitatory postsynaptic potentials (EPSPs), generated through DGC stimulation, can elicit burstlike responses in these neurons.
Metabotropic glutamate receptors and glutamate transporters shape transmission at the developing retinogeniculate synapse
Authors: Hauser Jessica L. , Edson Eleanore B. , Hooks Bryan M. , Chen Chinfei
Published: October 2012

Over the first few postnatal weeks, extensive remodeling occurs at the developing murine retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the visual thalamus. Although numerous studies have described the role of activity in the refinement of this connection, little is known about the mechanisms that regulate glutamate concentration at and around the synapse over development. Here we show that interactions between glutamate transporters and metabotropic glutamate receptors (mGluRs) dynamically control the peak and time course of the excitatory postsynaptic current (EPSC) at the immature synapse. Inhibiting glutamate transporters by bath application of TBOA (dl- threo-β-benzyloxyaspartic acid) prolonged the decay kinetics of both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) currents at all ages. Moreover, at the immature synapse, TBOA-induced increases in glutamate concentration led to the activation of group II/III mGluRs and a subsequent reduction in neurotransmitter release at RGC terminals. Inhibition of this negative-feedback mechanism resulted in a small but significant increase in peak NMDAR EPSCs during basal stimulation and a substantial increase in the peak with coapplication of TBOA. Activation of mGluRs also shaped the synaptic response during high-frequency trains of stimulation that mimic spontaneous RGC activity. At the mature synapse, however, the group II mGluRs and the group III mGluR7-mediated response are downregulated. Our results suggest that transporters reduce spillover of glutamate, shielding NMDARs and mGluRs from the neurotransmitter. Furthermore, mechanisms of glutamate clearance and release interact dynamically to control the glutamate transient at the developing retinogeniculate synapse.
Production, Purification, and Characterization of Polygalacturonase fromRhizomucor pusillusIsolated from Decomposting Orange Peels
Authors: Siddiqui Mohd. Asif , Pande Veena , Arif Mohammad
Published: October 2012

A thermophilic fungal strain producing polygalacturonase was isolated after primary screening of 40 different isolates. The fungus was identified asRhizomucor pusilisby Microbial Type Culture Collection (MTCC), Chandigarh, India. An extracellular polygalacturonase (PGase) fromR. pusiliswas purified to homogeneity by two chromatographic steps using Sephadex G-200 and Sephacryl S-100. The purified enzyme was a monomer with a molecular weight of 32 kDa. The PGase was optimally active at 55°C and at pH 5.0. It was stable up to 50°C for 120 min of incubation and pH condition between 4.0 and 5.0. The stability of PGase decreases rapidly above 60°C and above pH 5.0. The apparentKmandVmaxvalues were 0.22 mg/mL and 4.34 U/mL, respectively. It was the first time that a polygalacturonase enzyme was purified in this species. It would be worthwhile to exploit this strain for polygalacturonase production. Polygalacturonase from this strain can be recommended for the commercial production because of its constitutive and less catabolically repressive nature, thermostability, wide range of pH, and lowerKmproperties. However, scale-up studies are needed for the better output for commercial production.
Bladder Cancer in an Inguinoscrotal Vesical Hernia
Authors: Regis Lucas , Lozano Fernando , Planas Jacques , Morote Juan
Published: October 2012

We present the case of a 79-year-old male who, due to hematuria, underwent cystoscopy that showed a lesion in the bladder dome. Transurethral resection was attempted, but access to the tumor by this route was impossible. Given the findings, a body CT scan was performed showing an inguinoscrotal hernia with vesical carcinoma contained. Open surgical treatment of the vesical carcinoma contained within the inguinoscrotal hernia was performed in conjunction with the hernia repair. The anatomical pathology report confirmed a high-grade urothelial carcinoma (stage pT2b) with a free resection margin of <1 mm. Adjuvant radiotherapy was selected for subsequent treatment. The presence of bladder tumor in an inguinoscrotal hernia is an uncommon finding and a diagnostic delay can be assumed. The initial therapeutic plan may need to be changed from the usual approaches due to the atypical presentation.
Performance Analysis of IEEE 802.15.4 Compliant Wireless Devices for Heterogeneous Indoor Home Automation Environments
Authors: Nazabal Juan Antonio , Iturri Peio López , Azpilicueta Leire , Falcone Francisco , Fernández-Valdivielso Carlos
Published: October 2012

The influence of topology as well as morphology of complex indoor scenarios in the deployment of wireless sensor networks and wireless systems applied to home and building automation systems is analyzed. The existence of loss mechanisms such as material absorption (walls, furniture, etc.) and strong multipath components as well as the increase in the number of wireless sensors within indoor scenarios increases the relevance in the configuration of the heterogeneous wireless systems. Simulation results by means of empirical-based models are compared with an in-house 3D ray launching code as well as measurement results from wireless sensor networks illustrate the strong influence of the indoor scenario in the overall performance. The use of adequate radioplanning strategies lead to optimal wireless network deployments in terms of capacity, quality of service, and reduced power consumption.
The Influence of Obesity on Patient Reported Outcomes following Total Knee Replacement
Authors: Ayyar Vandana , Burnett Richard , Coutts Fiona J. , van der Linden Marietta L. , Mercer Thomas H.
Published: October 2012

This study retrospectively analysed the effects of obesity as described by Body Mass Index (BMI) on patient reported outcomes following total knee replacement. Participants (105 females and 66 males) who had undergone surgery under the care of a single surgeon were included in the review and were grouped according to their preoperative BMI into nonobese ( kg/m2), () obese ( kg/m2) (). Oxford Knee Score (OKS) and Short Form 12 scores (SF12) were taken preoperatively and 6 and 12 months after surgery to analyse differences between groups in the absolute scores as well as changes from before to after surgery. Preoperatively, the obese group had a significantly poorer OKS compared to non obese (44.7 versus 41.2, ). There were no statistically significant group effects on follow-up or change scores of the OKS and SF12. Correlations coefficients between BMI and follow-up and change scores were low (). There were no significant differences in the number of complications and revisions (local wound infection, 6.7% non obese, 11% obese, postoperative systemic complication, 8% non obese, 12% obese, revision, 4% nonobese, 3% obese). In conclusion, our findings indicate similar degrees of benefits from the surgery irrespective of patient BMI.
Quantitative Longitudinal Imaging of Vascular Inflammation and Treatment by Ezetimibe in apoE Mice by FMT Using New Optical Imaging Biomarkers of Cathepsin Activity and αvβ3 Integrin
Authors: Lin Shu-An , Patel Manishkumar , Suresch Donna , Connolly Brett , Bao Bagna , Groves Kevin , Rajopadhye Milind , Peterson Jeffrey D. , Klimas Michael , Sur Cyrille , Bednar Bohumil
Published: October 2012

Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of cathepsin proteases and the expression of αvβ3 integrin. We employed fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities using cathepsin sensing (ProSense, CatB FAST) and αvβ3 integrin (IntegriSense) near-infrared fluorescence (NIRF) agents. A statistically significant increase in the ProSense and IntegriSense signal was observed within the chest region of apoE−/− mice (P<0.05) versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet, respectively. In a treatment study using ezetimibe (7 mg/kg), there was a statistically significant reduction in the ProSense and CatB FAST chest signal of treated (P<0.05) versus untreated apoE−/− mice at 31 and 21 weeks on high cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated with macrophage counts and was found associated with inflammatory cells by fluorescence microscopy and flow cytometry of cells dissociated from aortas. This report demonstrates that cathepsin and αvβ3 integrin NIRF agents can be used as molecular imaging biomarkers for longitudinal detection of atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of ezetimibe with applications in preclinical testing of therapeutics and potentially for early diagnosis of atherosclerosis in patients.
Lung Radiofrequency Ablation: Potential as a Therapy to Oligometastasis and Oligo-Recurrence
Authors: Hiraki Takao , Kanazawa Susumu
Published: October 2012

The early results (e.g., patient survival) of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligo-recurrence or oligometastasis of lung cancer. The usefulness of RFA for oligo-recurrence or oligometastasis of lung cancer should be clarified by prospective studies in the future.
Some New Difference Inequalities and an Application to Discrete‐Time Control Systems
Authors: Zhou Hong , Huang Deqing , Wang Wu-Sheng , Xu Jian-Xin
Published: October 2012

Two new nonlinear difference inequalities are considered, where the inequalities consist of multiple iterated sums, and composite function of nonlinear function and unknown function may be involved in each layer. Under several practical assumptions, the inequalities are solved through rigorous analysis, and explicit bounds for the unknown functions are given clearly. Further, the derived results are applied to the stability problem of a class of linear control systems with nonlinear perturbations.
Entrapment Neuropathies in the Upper and Lower Limbs: Anatomy and MRI Features
Authors: Dong Qian , Jacobson Jon A. , Jamadar David A. , Gandikota Girish , Brandon Catherine , Morag Yoav , Fessell David P. , Kim Sung-Moon
Published: October 2012

Peripheral nerve entrapment occurs at specific anatomic locations. Familiarity with the anatomy and the magnetic resonance imaging (MRI) features of nerve entrapment syndromes is important for accurate diagnosis and early treatment of entrapment neuropathies. The purpose of this paper is to illustrate the normal anatomy of peripheral nerves in the upper and lower limbs and to review the MRI features of common disorders affecting the peripheral nerves, both compressive/entrapment and noncompressive, involving the suprascapular nerve, the axillary nerve, the radial nerve, the ulnar nerve, and the median verve in the upper limb and the sciatic nerve, the common peroneal nerve, the tibial nerve, and the interdigital nerves in the lower limb.
Vitamin E and Bone Structural Changes: An Evidence-Based Review
Authors: Naina Mohamed Isa , Borhanuddin Boekhtiar , Shuid Ahmad Nazrun , Mohd Fozi Nur Farhana
Published: October 2012

Purpose. This paper explores the effects of vitamin E on bone structural changes.Methods. A systematic review of the literature was conducted to identify relevant studies about vitamin E and osteoporosis/bone structural changes. A comprehensive search in Medline and CINAHL for relevant studies published between the years 1946 and 2012 was conducted. The main inclusion criteria were published in English, studies had to report the association or effect of vitamin E and osteoporosis-related bone changes, and the osteoporosis-related bone changes should be related to lifestyle variables, aging, or experimentally-induced conditions.Results. The literature search identified 561 potentially relevant articles, whereby 11 studies met the inclusion criteria. There were three human epidemiological studies and eight animal experimental studies included in this paper. Four animal studies reported positive bone structural changes with vitamin E supplementation. The rest of the studies had negative changes or no effect. Studies with positive changes reported better effects with tocotrienol vitamin E isomer supplementation.Conclusions. This evidence-based review underscores the potential of vitamin E being used for osteoporosis. The effect of one of the vitamin E isomers, tocotrienols, on bone structural changes warrants further exploration. Controlled human observational studies should be conducted to provide stronger evidence.
Online Projective Integral with Proper Orthogonal Decomposition for Incompressible Flows Past NACA0012 Airfoil
Authors: Sirisup Sirod , Maleewong Montri
Published: October 2012

The projective integration method based on the Galerkin-free framework with the assistance of proper orthogonal decomposition (POD) is presented in this paper. The present method is applied to simulate two-dimensional incompressible fluid flows past the NACA0012 airfoil problem. The approach consists of using high-accuracy direct numerical simulations over short time intervals, from which POD modes are extracted for approximating the dynamics of the primary variables. The solution is then projected with larger time steps using any standard time integrator, without the need to recompute it from the governing equations. This is called the online projective integration method. The results by the projective integration method are in good agreement with the full scale simulation with less computational needs. We also study the individual function of each POD mode used in the projective integration method. It is found that the first POD mode can capture basic flow behaviors but the overall dynamic is rather inaccurate. The second and the third POD modes assist the first mode by correcting magnitudes and phases of vorticity fields. However, adding the fifth POD mode in the model leads to some incorrect results in phase-shift forms for both drag and lift coefficients. This suggests the optimal number of POD modes to use in the projective integration method.
Effects of Temperature and Water-Filtered Infrared-A Alone or in Combination on Healthy and Glyoxal-Stressed Fibroblast Cultures
Authors: Knels Lilla , Valtink Monika , De la Vega Marin Jamlec , Steiner Gerald , Roehlecke Cora , Krueger Alexander , Funk Richard H. W.
Published: October 2012

Water-filtered infrared-A (wIRA) radiation has been described as supportive for tissue regeneration. We sought to investigate in detail the wIRA effect at different temperatures in 3T3 fibroblasts that were treated with glyoxal to induce formation of advanced glycation end products (AGEs). Nonirradiated and nonglyoxal-treated cells served as controls. Experiments were carried out over a range of 37∘–45∘C with exact temperature monitoring to distinguish between temperature and wIRA effects. Metabolic activity was assessed by resazurin assay. Mitochondrial membrane potential was assessed by JC-1 vital staining. Apoptotic changes were determined by vital staining with annexin V and YO-PRO-1 and determination of subG1 DNA content. Temperature had a dominant effect overriding effects exerted by wIRA or glyoxal treatment. The number of apoptotic cells was significantly higher at 45∘C, while the percentage of healthy cells was significantly lower at 45∘C. WIRA irradiation itself or in combination with glyoxal treatment exerted no damaging effects on the fibroblasts at physiological (37∘–40∘C) or higher (42∘–45∘C) temperatures compared to untreated controls. Temperatures of 45∘C, which can occur during inappropriate application of infrared irradiation, damage cells even in the absence of wIRA or glyoxal application.
The Value of Combined Large Format Histopathology Technique to Assess the Surgically Removed Breast Tissue following Neoadjuvant Chemotherapy: A Single Institution Study of 40 Cases
Authors: Ibarra Julio A.
Published: October 2012

Historically, neoadjuvant chemotherapy has been used to treat patients with advanced breast disease in an attempt to convert them into candidates for breast conservation surgery. The ultimate goal of histopathologic examination of the specimens removed after neoadjuvant chemotherapy is the identification of either residual disease or positive identification of the tumor bed. We report a series of 40 patients treated with neoadjuvant chemotherapy and evaluation of the surgical specimens by a combination of standard histopathology and the use of large format histopathology techniques.
Jumping to Conclusions Is Associated with Paranoia but Not General Suspiciousness: A Comparison of Two Versions of the Probabilistic Reasoning Paradigm
Authors: Moritz Steffen , Van Quaquebeke Niels , Lincoln Tania M.
Published: October 2012

Theoretical models ascribe jumping to conclusions (JTCs) a prominent role in the pathogenesis of paranoia. While many earlier studies corroborated this account, some newer investigations have found no or only small associations of the JTC bias with paranoid symptoms. The present study examined whether these inconsistencies in part reflect methodological differences across studies. The study was built upon the psychometric high-risk paradigm. A total of 1899 subjects from the general population took part in an online survey and were administered the Paranoia Checklist as well as one of two different variants of the probabilistic reasoning task: one variant with a traditional instruction (a) and one novel variant that combines probability estimates with decision judgments (b). Factor analysis of the Paranoia Checklist yielded an unspecific suspiciousness factor and a psychotic paranoia factor. The latter was significantly associated with scores indicating hasty decision making. Subjects scoring two standard deviations above the mean of the Paranoia Checklist showed an abnormal data-gathering style relative to subjects with normal scores. Findings suggest that the so-called decision threshold parameter is more sensitive than the conventional JTC index. For future research the specific contents of paranoid beliefs deserve more consideration in the investigation of decision making in schizophrenia as JTC seems to be associated with core psychosis-prone features of paranoia only.
Two Cases of Diffuse Duodenitis Associated with Ulcerative Colitis
Authors: Endo Katsuya , Kuroha Masatake , Shiga Hisashi , Kakuta Yoichi , Takahashi Seiichi , Kinouchi Yoshitaka , Shimosegawa Tooru
Published: October 2012

The upper gastrointestinal tract is not generally considered a target organ in ulcerative colitis (UC). However, several cases showing upper gastrointestinal involvement in UC have been reported. In this report, we present 2 rare cases of diffuse duodenitis accompanying pancolonic UC. Case patient 1 was a 44-year-old man who developed diffuse duodenitis shortly after colectomy and was successfully treated with mesalazine. Case patient 2 was a 25-year-old woman who developed diffuse duodenitis under a steroid-free condition and was successfully treated with prednisolone. The 2 patients hadHelicobacter pylori-negative duodenitis that resembled colonic lesions of UC in both the endoscopic and histological findings. No evidence of Crohn’s disease was found in these cases. We diagnosed both cases as typical UC-associated diffuse duodenitis. The occurrence of gastrointestinal involvement in UC has been attracting attention because such lesions could potentially open a new window for studying the etiology and pathogenesis of UC. Further studies involving a large number of patients are needed to clarify whether the upper gastrointestinal tract is a target organ in UC.
A Call for the Aggressive Treatment of Oligometastatic and Oligo-Recurrent Non-Small Cell Lung Cancer
Authors: Patel Pretesh R. , Yoo David S. , Niibe Yuzuru , Urbanic James J. , Salama Joseph K.
Published: October 2012

Metastatic non-small cell lung cancer (NSCLC) carries a dismal prognosis. Clinical evidence suggests the existence of an intermediate, or oligometastatic, state when metastases are limited in number and/or location. In addition, following initial curative therapy, many patients present with limited metastatic disease, or oligo-recurrence. Metastasis-directed, anti-cancer therapies may benefit these patients. A growing evidence-base supports the use of hypofractionated, image-guided radiotherapy (HIGRT) for a variety of malignant conditions including inoperable stage I NSCLC and many metastatic sites. When surgical resection is not possible, HIGRT offers an effective alternative for local treatment of limited metastatic disease. Early studies have produced promising results when HIGRT was delivered to all known sites of disease in patients with oligometastatic/oligo-recurrent NSCLC. In a population of patients formerly considered rapidly terminal, these studies report five year overall survival rates of 13–22%. HIGRT for metastatic NSCLC warrants further study. We call for large, intergroup, and even international randomized trials incorporating HIGRT and other metastasis-directed therapies into the treatment of patients with oligometastatic/oligo-recurrent NSCLC.
Multiple Roles for VEGF in Non-Melanoma Skin Cancer: Angiogenesis and Beyond
Authors: Johnson Kelly E. , Wilgus Traci A.
Published: October 2012

Vascular endothelial growth factor (VEGF) is known to play a critical role in the development of non-melanoma skin cancers. VEGF is a potent pro-angiogenic factor and it is elevated in mouse and human skin tumors. The use of transgenic and knockout mice has shown that VEGF is essential for tumor development in multiple models of skin carcinogenesis and, until recently, the mechanism of action has been primarily attributed to the induction of angiogenesis. However, additional roles for VEGF have now been discovered. Keratinocytes can respond directly to VEGF, which could influence skin carcinogenesis by altering proliferation, survival, and stemness.In vivostudies have shown that loss of epidermal VEGFR-1 or neuropillin-1 inhibits carcinogenesis, indicating that VEGF can directly affect tumor cells. Additionally, VEGF has been shown to promote tumor growth by recruiting macrophages to skin tumors, which likely occurs through VEGFR-1. Overall, these new studies show that VEGF carries out functions beyond its well-established effects on angiogenesis and highlight the need to consider these alternative activities when developing new treatments for non-melanoma skin cancer.
Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model
Authors: Yamada Takaya , Tongu Miki , Goda Kaoru , Aoi Noriaki , Morikura Ichiro , Fuchiwaki Takafumi , Kawauchi Hideyuki
Published: October 2012

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4+CD25−effector T cellsin vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.
Dedifferentiated Leiomyosarcoma of the Uterus with Heterologous Elements: A Potential Diagnostic Pitfall
Authors: Rawish Kojo R. , Fadare Oluwole
Published: October 2012

Dedifferentiation is a phenomenon that is well characterized in a variety of tumors and is defined by the occurrence of a high-grade or undifferentiated tumor, typically unrecognizable regarding its line of differentiation, from a low-grade/borderline neoplasm. This phenomenon has previously been described in 2 uterine leiomyosarcomas, but both were devoid of heterologous elements. The authors describe herein a case of a dedifferentiated leiomyosarcoma of the uterus with osteoid heterologous elements, believed to be the first such reported case. The original tumor was a high-grade leiomyosarcoma with large low-grade and leiomyoma-like areas and whose constituent cells displayed intense nuclear immunoreactivity for both estrogen receptor (ER) and progesterone receptor (PR) in approximately 30% of cells. The tumor recurred six months after its resection as an undifferentiated sarcoma that was negative for smooth muscle markers, but which remained positive for ER and PR. Osteoid production was only identified in the recurrent tumor and was significant in extent therein. This case highlights the immunophenotypic changes that may occur in dedifferentiated leiomyosarcomas, and this possibility should be a consideration when an apparently undifferentiated sarcoma is identified in a patient with a history of uterine leiomyosarcoma. In our case, the expression of ER and PR provided significant supportive evidence of the uterine origin of the recurrent tumor.
The Cost of Medicaid Savings: The Potential Detrimental Public Health Impact of Neonatal Circumcision Defunding
Authors: Andrews Annie L. , Lazenby Gweneth B. , Unal Elizabeth Ramsey , Simpson Kit N.
Published: October 2012

Objective. To project the increased incidence of HIV and subsequent costs resulting from the expected decreased rate of circumcision due to Medicaid defunding in one southeastern state.Methods. Using 2009 South Carolina (SC) Medicaid birth cohort (n=29,316), we calculated expected heterosexually acquired HIV cases at current circumcision rates. To calculate age/race/gender specific HIV incidence rates, we used 2009 South Carolina Department of Health and Environmental Control reported gender and race specific HIV cases, CDC reported age distribution of HIV cases, and 2009 S.C. population data. Accounting for current circumcision rates, we calculated the change in incidence of heterosexually acquired HIV assuming circumcision provides 60% protection against HIV transmission to males and 46% protection against male to female transmission. Published lifetime cost of HIV was used to calculate the cost of additional HIV cases.Results. Assuming Medicaid circumcision rates decrease from current nationally reported levels to zero secondary to defunding, we project an additional 55 male cases of HIV and 47 female cases of HIV among this birth cohort. The total cost discounted to time of infection of these additional HIV cases is $20,924,400 for male cases and $17,711,400 for female cases. The cost to circumcise males in this birth cohort at currently reported rates is $4,856,000.Conclusions. For every year of decreased circumcision rates due to Medicaid defunding, we project over 100 additional HIV cases and $30,000,000 in net medical costs.
Osseous Metaplasia and Bone Marrow Elements in a Case of Renal Cell Carcinoma
Authors: Ozkanli Seyma , Yildirim Asif , Zemheri Ebru , Keskin Sarp Korcan , Basok Erem Kaan
Published: October 2012

Renal cell carcinoma with osseous metaplasia and bone marrow elements is a relatively rare event in these tumors. We discuss pathological differential diagnosis for this tumor with a review of the literature on this unusual case.
Gene Transfer of Heme Oxygenase-1 Using an Adeno-Associated Virus Serotype 6 Vector Prolongs Cardiac Allograft Survival
Authors: Evans Jacqueline M. , Navarro Sonia , Doki Tomoko , Stewart John M. , Mitsuhashi Noboru , Kearns-Jonker Mary
Published: October 2012

Introduction. Allograft survival can be prolonged by overexpression of cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector design and delivery have provided new opportunities to safely and effectively administer HO-1 into the heart prior to transplantation to improve long-term graft outcome.Methods. HO-1 was delivered to the donor heart using an adeno-associated virus vector (AAV) with a pseudotype 6 capsid and vascular endothelial growth factor (VEGF) to enhance myocardial tropism and microvascular permeability. Survival of mouse cardiac allografts, fully or partially mismatched at the MHC, was determined with and without cyclosporine A. Intragraft cytokine gene expression was examined by PCR.Results. The use of AAV6 to deliver HO-1 to the donor heart, combined with immunosuppression, prolonged allograft survival by 55.3% when donor and recipient were completely mismatched at the MHC and by 94.6% if partially mismatched. The combination of gene therapy and immunosuppression was more beneficial than treatment with either AAV6-HO-1 or CsA alone. IL-17a, b, e and f were induced in the heart at rejection.Conclusions. Pretreatment of cardiac allografts with AAV6-HO-1 plus cyclosporine A prolonged graft survival. HO-1 gene therapy represents a beneficial adjunct to immunosuppressive therapy in cardiac transplantation.
Nonepiphyseal Giant Cell Tumor of the Rib: A Case Report
Authors: Moschouris Hippocrates , Marinis Athanasios , Bouma Evanthia , Karagiannis Evangelos , Kiltenis Michalis , Papadaki Marina
Published: October 2012

A case of a 32-year-old female patient with a giant cell tumor originating in the middle part of the left 10th rib is presented. On X-rays and CT, the tumor caused a well-defined osteolysis with nonsclerotic borders. On MRI, it exhibited intermediate signal intensity on T1 sequences and central high signal and peripheral intermediate signal on T2 sequences. On contrast-enhanced MR images both central and peripheral-periosteal enhancement was noted. Thanks to its small size ( cm), the lesion was easily resected en bloc with a part of the affected rib. The patient is free of recurrence for 3 years after the operation.