bluuebunny/crossref_metadata_2025 huggingface dataset:
Heme oxygenase: the key to renal function regulation
Authors: Abraham Nader G. , Cao Jian , Sacerdoti David , Li Xiaoying , Drummond George
Published: July 2009

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function.
Higher intramuscular triacylglycerol in women does not impair insulin sensitivity and proximal insulin signaling
Authors: Høeg Louise , Roepstorff Carsten , Thiele Maja , Richter Erik A. , Wojtaszewski Jørgen F. P. , Kiens Bente
Published: July 2009

Women have been shown to have higher muscle triacylglycerol (IMTG) levels than men and could therefore be expected to have lower insulin sensitivity than men, since previous studies have linked high IMTG to decreased insulin sensitivity. Therefore, insulin sensitivity of whole body and leg glucose uptake was studied in 9 women in the follicular phase and 8 men on a controlled diet and matched for maximal oxygen uptake per kilogram of lean body mass and habitual activity level. A 47% higher ( P < 0.05) IMTG level was found in women than in men, and, at the same time, women also displayed 22% higher whole body insulin sensitivity ( P < 0.05) and 29% higher insulin-stimulated leg glucose uptake ( P = 0.05) during an euglycemic-hyperinsulinemic (≈70 μU/ml) clamp compared with matched male subjects. The higher insulin sensitivity in women could not be explained by higher expression of muscle glucose transporter GLUT4, insulin receptor, or Akt expression or by the ability of insulin to stimulate Akt Thr308 or Akt Ser473 phosphorylation. However, a 30% higher ( P < 0.05) capillary density and 31% more type 1 muscle fiber expressed per area in the vastus lateralis muscle were noted in women than in matched men. It is concluded that despite 47% higher IMTG levels in women in the follicular phase, whole body as well as leg insulin sensitivity are higher than in matched men. This was not explained by sex differences in proximal insulin signaling in women. In women, it seems that a high capillary density and type 1 muscle fiber expression may be important for insulin action.
Gravity Dependence of Subjective Visual Vertical Variability
Authors: Tarnutzer A. A. , Bockisch C. , Straumann D. , Olasagasti I.
Published: July 2009

The brain integrates sensory input from the otolith organs, the semicircular canals, and the somatosensory and visual systems to determine self-orientation relative to gravity. Only the otoliths directly sense the gravito-inertial force vector and therefore provide the major input for perceiving static head-roll relative to gravity, as measured by the subjective visual vertical (SVV). Intraindividual SVV variability increases with head roll, which suggests that the effectiveness of the otolith signal is roll-angle dependent. We asked whether SVV variability reflects the spatial distribution of the otolithic sensors and the otolith-derived acceleration estimate. Subjects were placed in different roll orientations (0–360°, 15° steps) and asked to align an arrow with perceived vertical. Variability was minimal in upright, increased with head-roll peaking around 120–135°, and decreased to intermediate values at 180°. Otolith-dependent variability was modeled by taking into consideration the nonuniform distribution of the otolith afferents and their nonlinear firing rate. The otolith-derived estimate was combined with an internal bias shifting the estimated gravity-vector toward the body-longitudinal. Assuming an efficient otolith estimator at all roll angles, peak variability of the model matched our data; however, modeled variability in upside-down and upright positions was very similar, which is at odds with our findings. By decreasing the effectiveness of the otolith estimator with increasing roll, simulated variability matched our experimental findings better. We suggest that modulations of SVV precision in the roll plane are related to the properties of the otolith sensors and to central computational mechanisms that are not optimally tuned for roll-angles distant from upright.
P2 Receptor–Mediated Signaling in Spherical Bushy Cells of the Mammalian Cochlear Nucleus
Authors: Milenkovic Ivan , Rinke Ilka , Witte Mirko , Dietz Beatrice , Rübsamen Rudolf
Published: July 2009

Purinoreceptors of the P2 family contribute strongly to signaling in the cochlea, but little is known about the effects of purinergic neurotransmission in the central auditory system. Here we examine P2 receptor–mediated signaling in the large spherical bushy cells (SBCs) of Mongolian gerbils around the onset of acoustically evoked signal processing (P9–P14). Brief adenosine 5′-O-(3-thiotriphosphate) (ATPγS) application evoked inward current, membrane depolarization, and somatic Ca2+signals. Moreover, ATPγS changed the SBCs firing pattern from phasic to tonic, when the application was synchronized with depolarizing current injection. This bursting discharge activity was dependent on [Ca2+]iand Ca2+-dependent protein kinase (PKC) activity and is presumably caused by modulation of low-threshold K+conductance. Activation of P2Y1receptors could not evoke these changes per se, thus it was concluded that the involvement of P2X receptors seems to be necessary. Ca2+imaging data showed that both P2X and P2Y1receptors mediate Ca2+signals in SBCs where P2Y1receptors most likely activate the PLC–IP3(inositol trisphosphate) pathway and release Ca2+from internal stores. Immunohistochemical staining confirmed the expression of P2X2and P2Y1receptor proteins in SBCs, providing additional evidence for the involvement of both receptors in signal transduction in these neurons. Purinergic signaling might modulate excitability of SBCs and thereby contribute to regulation of synaptic strength. Functionally, the increase in firing rate mediated by P2 receptors could reduce temporal precision of the postsynaptic firing, e.g., phase locking, which has an immediate effect on signal processing related to sound localization. This might provide a mechanism for adaptation to the ambient acoustic environment.
Endocannabinoids Mediate Tachykinin-Induced Effects in the Lamprey Locomotor Network
Authors: Thörn Pérez Carolina , Hill Russell H. , Manira Abdeljabbar El. , Grillner Sten
Published: July 2009

The spinal network underlying locomotion in lamprey is composed of excitatory and inhibitory interneurons mediating fast ionotropic action. In addition, several modulator systems are activated as locomotion is initiated, including the tachykinin system and the metabotropic glutamate receptor 1 (mGluR1), the latter operating partially via the endocannabinoid system. The effects of mGluR1 agonists and tachykinins resemble each other. Like mGluR1 agonists, the tachykinin substance P accelerates the burst rate and reduces the crossed inhibition in an activity-dependent fashion. The present study therefore explores whether tachykinins also use the endocannabinoid system to modulate the locomotor frequency. By monitoring fictive locomotion, we were able to compare the facilitatory effects exerted by applying substance P (1 μM, 20 min), on the burst frequency before and during application of the endocannabinoid CB1 receptor antagonist AM251 (2–5 μM). By using two different lamprey species, we showed that the response to substance P on the burst frequency is significantly reduced during the application of AM251. To examine whether endocannabinoids are involved in the substance P–mediated modulation of reciprocal inhibition, the commissural axons were stimulated, while recording intracellularly from motoneurons. We compare the effect of substance P on the amplitude of the contralateral compound glycinergic inhibitory postsynaptic potential (IPSP) in control and in the presence of AM251. The blockade of CB1 receptors reduced the substance P–mediated decrease in the amplitude by 29%. The present findings suggest that the effects of substance P on the increase in the locomotor burst frequency and depression of IPSPs are mediated partially via release of endocannabinoids acting through CB1 receptors.
Is the Insula the “How Much” Intensity Coder?
Authors: Moayedi Massieh , Weissman-Fogel Irit
Published: July 2009

The perception of all sensations includes some sort of magnitude estimate used to calibrate behavior. However, it is not known whether unique intensity coding mechanisms exist for specific modalities or whether a common, centralized magnitude estimator operates for all sensations. Here, we discuss findings regarding pain intensity coding and the role of the insula in pain in light of the recent article by Baliki and colleagues that proposes the insula as a multimodal magnitude estimator.
Auditory Spatial Tuning at the Crossroads of the Midbrain and Forebrain
Authors: Pérez M. Lucía , Shanbhag Sharad J. , Peña José Luis
Published: July 2009

The barn owl's midbrain and forebrain contain neurons tuned to sound direction. The spatial receptive fields of these neurons result from sensitivity to combinations of interaural time (ITD) and level (ILD) differences over a broad frequency range. While a map of auditory space has been described in the midbrain, no similar topographic representation has been found in the forebrain. The first nuclei that belong exclusively to the forebrain and midbrain pathways are the thalamic nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. The midbrain projects to the auditory thalamus before sharp spatial receptive fields emerge; although Ov and ICx receive projections from the same midbrain nuclei, they are not directly connected. We compared the spatial tuning in Ov and ICx. Thalamic neurons respond to a broader frequency range and their ITD and ILD tuning varied more across frequency. However, neurons in Ov showed spatial receptive fields as selective as neurons in ICx. Thalamic spatial receptive fields were tuned to frontal and contralateral space and correlated with their tuning to ITD and ILD. Our results indicate that spatial tuning emerges in both pathways by similar combination selectivity to ITD and ILD. However, the midbrain and the thalamus do not appear to repeat exactly the same processing, as indicated by the difference in frequency range and the broader tuning to binaural cues. The differences observed at the initial stages of these sound-localization pathways may reflect diverse functions and coding schemes of midbrain and forebrain.
Control of a Depolarizing GABAergic Input in an Auditory Coincidence Detection Circuit
Authors: Tang Zheng-Quan , Gao Hongxiang , Lu Yong
Published: July 2009

Neurons in the chicken nucleus laminaris (NL), the third-order auditory neurons that detect the interaural time differences that enable animals to localize sounds in the horizontal plane, receive glutamatergic excitation from the cochlear nucleus magnocellularis (NM) and GABAergic inhibition from the ipsilateral superior olivary nucleus. Here, we study metabotropic glutamate receptor (mGluR)- and GABABreceptor (GABABR)-mediated modulation of synaptic transmission in NL neurons. Gramicidin-perforated recordings from acute brain stem slice preparations showed that the reversal potential of the GABAergic responses in NL neurons was more depolarized than the spike threshold. Activation of the GABAergic input produced a mix of inhibitory and excitatory actions in NL neurons. The inhibitory action is known to be critical in improving the acuity of temporal processing of sounds. The excitatory action, however, would reduce the phase locking fidelity of NL neurons in response to their excitatory inputs from the NM. We show that activation of presynaptic mGluRs or GABABRs by either exogenous agonists or synaptically released neurotransmitters reduced the GABAergic responses, preventing the excitatory action of GABA while leaving the inhibitory action intact. Unlike most CNS synapses, the glutamatergic transmission in the NL was not modulated by either mGluRs or GABABRs, indicating that fixed (nonmodulatory) excitatory inputs to the NL may be optimal for coincidence detection. This study contributes to our understanding of how selective neuromodulation is achieved to suit a particular function of neuronal circuits in the brain.
Oscillations in the Basolateral Amygdala: Aversive Stimulation Is State Dependent and Resets the Oscillatory Phase
Authors: Crane James W. , Windels Francois , Sah Pankaj
Published: July 2009

Slow oscillations (<1 Hz) in neural activity occur during sleep and quiet wakefulness in both animals and humans. Here we show that in urethan-anesthetized animals, neurons in the basolateral amygdala in vivo display a slow oscillation between resting membrane potential (down-state) and depolarized potentials (up-states) occurring at a frequency of ∼0.3 Hz. This oscillation is insensitive to the holding potential and continues unabated under voltage clamp, indicating that up-states are synaptically driven. Somatosensory stimulation (footshock) delivered during the down-state evoked an all-or-none transition into an up-state. When delivered during down-states, footshocks triggered up-states and reset the phase of the neural oscillation, effectively synchronizing activity in the basolateral amygdala. This phase reset was reproduced by posterior thalamus stimulation, confirming that it was mediated by aversive sensory input. In contrast, a footshock delivered during the up-state was ineffective in stimulating BLA neurons. We conclude that oscillatory activity in the basolateral amygdala is driven by ensembles of cortical neurons. These ensembles gate the response of amygdala neurons to aversive stimulation in a state-dependent manner. Aversive stimulation is effective when the network is in the down-state but ineffective when the network is in an up-state.
Sensory-Encoding Differences Contribute to Species-Specific Call Recognition Mechanisms
Authors: Triblehorn J. D. , Schul J.
Published: July 2009

Object recognition is a fundamental function of the auditory system, but the underlying mechanisms are not well understood. Acoustic communication in the Tettigoniid genus Neoconocephalus provides a useful system for studying these mechanisms. We examined the ascending interneuron pathway in three Neoconocephalus species with diverse calls and recognition mechanisms. This pathway processes spectral information and transmits call temporal patterns to the supraesophageal ganglion where the recognition circuits reside. For each species, we describe one local auditory interneuron (ON) and three with ascending projections (AN-1, AN-2, TN-1), which were physiologically and morphologically similar to those described in other Tettigoniids. TN-1 responded only to the beginning of call models. For AN-1, each call model pulse elicited a single action potential in N. robustus and N. bivocatus, whereas every other pulse elicited an action potential in N. triops. Individual pulses did not reliably evoke AN-2 responses in all three species. AN-1 responses were limited to frequencies <20 kHz. AN-1 tuning differed among the three species, reflecting their differences in the dominant frequency of the calls. AN-2 was broadly tuned, and responses increased with intensity in all three species. In behavioral experiments, N. robustus showed greater spectral selectivity than the other two species. Adding the second harmonic to the spectrum of call models suppressed phonotaxis in N. robustus, but not N. triops or N. bivocatus. Adding the second harmonic reduced AN-1 responses in N. robustus but not in the other two species. We discuss the potential function of the ascending neurons for call recognition.
Sex Disparity in Food Allergy: Evidence from the PubMed Database
Authors: Kelly Caleb , Gangur Venu
Published: July 2009

Food allergies are potentially fatal immune-mediated disorders that are growing globally. The relationship between sex and food allergy remains incompletely understood. Here we tested the hypothesis that, should sex influence the clinical response to food allergens, this would be reflected by a sex disparity in published studies of food allergy. We performed a systematic search of the PubMed literature for IgE-mediated allergy to 11 allergenic foods of international regulatory importance. No date restriction was used and only articles in English were considered. Of the 4744 articles retrieved, 591 met the inclusion criteria representing 17528 subjects with food allergies. Whereas among children with food allergies, 64.35% were males and 35.65% were females (male/female ratio, 1.80), among adults 34.82% were males and 65.18% were females (male/female ratio, 0.53). Consequently, these data argue that there is need for further investigation to define the role of sex in the pathogenesis of food allergy.
Sharp Condition for Global Existence and Blow‐Up on Klein‐Gordon Equation
Authors: Junsheng Zhao , Shufeng Li
Published: July 2009

We study the initial boundary value problem of the nonlinear Klein‐Gordon
equation. First we introduce a family of potential wells. By using them, we obtain a
new existence theorem of global solutions and show the blow‐up in finite time of solutions.
Especially the relation between the above two phenomena is derived as a sharp condition.
Analyzing Spur‐Distorted Impedance Spectra for the QCM
Authors: Yoon Sae Moon , Cho Nam Joon , Kanazawa Kay
Published: July 2009

The quartz crystal microbalance (QCM) is a sensitive device for determining the properties of materials loading it. One of the fundamental means of making these measurements is the so‐called impedance (or admittance) spectra method. The resonant properties of the piezoelectric QCM sensor are measured
over a spectral range in the neighborhood of a resonance, both with load and without load. The changes
in the spectrum upon loading can be compared to models that describe the changes based on the mass
density, the shear modulus, and the viscosity of the load. This comparison can be made with confidence
so long as the spectrum corresponds to the model assumption of a single main resonance.
Often, there exists a spurious resonance lying above the main resonance which is not included in the
models. This can change the shape of the spectrum in ways not included in the model analysis. We
describe a method we have used that separates the spur resonance from the main resonance,
permitting the parameters of the main resonance to be isolated from that of the spur. These corrected
parameters of the main resonance can then be used with confidence in model analyses.
Some Results on Bellman Equations of Optimal Production Control in a Stochastic Manufacturing System
Authors: Baten Azizul , Kamil Anton Abdulbasah
Published: July 2009

The paper studies the production inventory problem of minimizing
the expected discounted present value of production cost control in a manufacturing system with degenerate stochastic demand. We establish the existence of a
unique solution of the Hamilton‐Jacobi‐Bellman (HJB) equations associated with
this problem. The optimal control is given by a solution to the corresponding HJB
equation.
Strong Convergence of a New Iteration for a Finite Family of Accretive Operators
Authors: Hu Liang-Gen , Wang Jin-Ping
Published: July 2009

The viscosity approximation methods are employed to establish strong convergence of the modified Mann iteration scheme to a common zero of a finite family of accretive operators on a strictly convex Banach space with uniformly Gâteaux differentiable norm. Our work improves and extends various results existing in the current literature.
Regression Test Selection for C# Programs
Authors: Mansour Nashat , Statieh Wael
Published: July 2009

We present a regression test selection technique for C# programs. C# is fairly new and is often used within the Microsoft .Net framework to give programmers a solid base to develop a variety of applications. Regression testing is done after modifying a program. Regression test selection refers to selecting a suitable subset of test cases from the original test suite in order to be rerun. It aims to provide confidence that the modifications are correct and did not affect other unmodified parts of the program. The regression test selection technique presented in this paper accounts for C#.Net specific features. Our technique is based on three phases; the first phase builds an Affected Class Diagram consisting of classes that are affected by the change in the source code. The second phase builds a C# Interclass Graph (CIG) from the affected class diagram based on C# specific features. In this phase, we reduce the number of selected test cases. The third phase involves further reduction and a new metric for assigning weights to test cases for prioritizing the selected test cases. We have empirically validated the proposed technique by using case studies. The empirical results show the usefulness of the proposed regression testing technique for C#.Net programs.
Stochastic Differential Equation‐Based Flexible Software Reliability Growth Model
Authors: Kapur P. K. , Anand Sameer , Yamada Shigeru , Yadavalli Venkata S. S.
Published: July 2009

Several software reliability growth models (SRGMs) have been developed by software developers in tracking and measuring the growth of reliability. As the size of software system is large and the number of faults detected during the testing phase becomes large, so the change of the number of faults that are detected and removed through each debugging becomes sufficiently small compared with the initial fault content at the beginning of the testing phase. In such a situation, we can model the software fault detection process as a stochastic process with continuous state space. In this paper, we propose a new software reliability growth model based on Itô type of stochastic differential equation. We consider an SDE‐based generalized Erlang model with logistic error detection function. The model is estimated and validated on real‐life data sets cited in literature to show its flexibility. The proposed model integrated with the concept of stochastic differential equation performs comparatively better than the existing NHPP‐based models.
A Cross‐Layer Framework for Efficient Streaming of H.264 Video over IEEE 802.11 Networks
Authors: Moid Azfar , Fapojuwo Abraham O.
Published: July 2009

This paper presents a framework for reliable and efficient streaming of H.264 video over an IEEE 802.11‐based wireless network. The framework relies on a cross‐layer mechanism that jointly adapts the video transcoding parameters at the application layer and the video transmission parameters at the data‐link layer to the network conditions defined by buffer length and wireless propagation channel. The effectiveness of the proposed framework is demonstrated through the transmission of three test video sequences (Akiyo, Container, and Foreman) having different degrees of motion over an IEEE802.11 wireless network. Simulation results show that the proposed cross‐layer‐based framework provides an enhancement of up to 3 dB in the video quality with a negligible increase (<5%) in the packet processing time. Hence, the proposed framework achieves a good balance in the tradeoff between video quality and packet processing time. The proposed framework, along with its performance results, provides valuable insights on the selection of network parameter values for efficient and reliable transmission of video applications in wireless networks.
Highly Sensitive InOx Ozone Sensing Films on Flexible Substrates
Authors: Kiriakidis G. , Moschovis K. , Kortidis I. , Skarvelakis R.
Published: July 2009

InOx thin films with a thickness of the order of 100 nm were grown by dc magnetron sputtering on glass, Si and flexible (PET) substrates. The electrical conductivity of InOx thin films exhibited a change of two orders of magnitude during photoreduction with ultraviolet light and subsequent oxidation in ozone concentrations from 2370 to 15 ppb, at room temperature. Optical transparency of over 85% for all substrates was maintained. Film structural and ozone sensing properties were analyzed. Surface morphology investigations carried out by SEM for films on PET substrates showed extended surface cracking for bending angles beyond 40∘. Optimization of growth conditions has led to films with extremely low detection levels for ozone down to 15 ppb at room temperature, demonstrating the wide prospective of utilizing these metal oxides as gas sensors on flexible substrates for a variety of automotive and air‐conditioning applications.
Synthesis and Characterization of bis[(2‐ethyl‐5‐methyl‐imidazo‐4‐yl)methyl]Sulfide and Its Coordination Behavior toward Cu(II) as a Possible Approach of a Copper Site Type I
Authors: Barrón-Garcés Juan D. , Mendoza-Díaz Guillermo , Vilchez-Aguado Florina , Bernès Sylvain
Published: July 2009

The synthesis and characterization of a novel ligand, bis[(2‐ethyl‐5‐methyl‐imidazo‐4‐yl)methyl]sulfide (bemims), as well as a bemims‐containing copper(II) coordination complex are described. In this complex, [Cu(bemims)X2] with X = NO3 −, bemims acts as a tridentate ligand and two monodentate nitrate ions complete the coordination sphere. Both imidazole N atoms and the thioether S atom of bemims participate in coordination. The Cu(II) ion is five‐coordinated with a slightly distorted square‐pyramidal geometry (τ = .09). Electrochemical studies and spectroscopic data for this complex are compared with some blue copper proteins in order to assess its ability to mimic the copper center of type I copper proteins.
Blood Galactose and Glucose Levels in Mothers, Cord Blood, and 48-Hour-Old Breast-Fed Full-Term Infants
Authors: Bossolan Grasiela , Trindade Cleide E.P. , Barreiros Rodrigo Crespo
Published: July 2009

Background: Although galactose is an important component in human lactose, there are few reports of its role in the newborn metabolism. Objective: To determine the relationship of blood galactose and glucose levels in mothers, cord blood, and breast-fed full-term newborn infants. Methods: Maternal and cord vein blood samples were obtained from 27 pregnant women at delivery, and from their breast-fed, full-term newborns 48 h later. Galactose and glucose were determined by HPLC. Statistical analysis used ANOVA and Pearson correlation with p < 0.05. Results: Maternal galactose concentrations (0.08 ± 0.03 mmol/l) were similar to cord blood galactose (0.07 ± 0.03 mmol/l; p = 0.129). However, newborn blood galactose (0.05 ± 0.02 mmol/l) was significantly lower than both cord (p = 0.042) and maternal blood (p = 0.002). Maternal blood glucose levels (4.72 ± 0.86 mmol/l) were higher than cord blood (3.98 ± 0.57 mmol/l; p < 0.001), and cord blood concentrations were higher than newborn blood levels (3.00 ± 0.56 mmol/l; p < 0.001); all values expressed as mean ± SD. Significant correlation was only seen between maternal and cord blood galactose levels (r = 0.67; p < 0.001) and glucose levels (r = 0.38; p = 0.047). Conclusion: The association and similarity between maternal and cord blood galactose levels suggest that the fetus is dependent on maternal galactose. In contrast, the lower galactose levels in newborn infants and a lack of association between both suggest self-regulation and a dependence on galactose ingestion.
Cardiac Troponin I Degradation in Serum of Patients with Hypertrophic Obstructive Cardiomyopathy Undergoing Percutaneous Septal Ablation
Authors: Madsen Lene H. , Lund Terje , Grieg Zanina , Nygaard Ståle , Holmvang Lene , Jurlander Birgit , Grande Peer , Christensen Geir , Atar Dan
Published: July 2009

Introduction: Troponin has become the most important marker for diagnosing acute myocardial infarction, yet knowledge is scarce regarding appearance of specific degradation fragments in the blood. We have recently described the appearance of intact cardiac troponin I (cTnI) and 7 degradation products in patients suffering from ST-elevation myocardial infarction (STEMI) using Western blot analysis. However, the time resolution in STEMI patients is hampered by the rather vague time point ‘onset of pain’. We therefore sought to utilize a time-wise more reliable model of human myocardial necrosis: percutaneous transluminal septal myocardial ablation (PTSMA) of hypertrophic obstructive cardiomyopathy (HOCM). Here the iatrogenic induction of myocardial necrosis occurs in vivo, allowing us to investigate degradation of cTnI by the second. Methods: Blood samples were obtained from 8 patients with HOCM just prior to initiation of PTSMA and up to 50 h following the procedure. Western blot analysis was performed with subsequent analysis of relative intensities of the bands as compared to the degradation of cTnI in STEMI patients from the ASSENT-2 troponin substudy. Results: We demonstrate intact cTnI and 9 degradation products [molecular weight (MW) 12.0–23.5 kDa]. The bands were comparable in MW to degradation fragments in STEMI. Their early rise in intensity, occurring within few minutes after the alcohol injection, emphasizes how susceptible troponin bands are to chemical/ischemic insults. Moreover, two additional bands were visible in the PTSMA population. Conclusion: This work describes the degradation products of troponin I in HOCM patients undergoing PTSMA. The detected bands appear fast and are similar to degradations following STEMI. This model contributes to our knowledge of the degradation patterns of troponin in disease states, and may thus play a role in the interpretation of elevated troponin levels.
Comparison of Three Different Optical Coherence Tomography Models for Total Macular Thickness Measurements in Healthy Controls
Authors: Menke Marcel N. , Dabov Simeon , Sturm Veit
Published: July 2009

Background/Aims: Conventional time domain optical coherence tomography (OCT) has become an important diagnostic tool to measure retinal thickness in clinical routine. Recently, different models of high-speed, high-resolution frequency domain OCTs have been introduced by various manufacturers. The purpose of this study was to compare 3 commercially available OCT models for retinal thickness measurements in healthy controls. Methods: OCT scans were performed on 28 healthy eyes with the RTVue-100 FD-OCT (Optovue Inc., USA), the Cirrus™ HD-OCT (Carl Zeiss Meditec Inc., USA) and the Stratus OCT 3000 (Carl Zeiss Meditec Inc.). Retinal thickness values were calculated and compared between OCT models. Results: Differences in mean retinal thickness measurements between OCT models were statistically significant. Mean retinal thickness measurement with Cirrus OCT, RTVue OCT and with Stratus OCT was 300, 265 and 257 μm, respectively. Conclusion: Measurements with different OCT models lead to significantly different retinal thickness values.
Tachyphylaxis after Repeated Antidepressant Drug Exposure in Patients with Recurrent Major Depressive Disorder
Authors: Amsterdam Jay D. , Williams David , Michelson David , Adler Lenard A. , Dunner David L. , Nierenberg Andrew A. , Reimherr Frederick W. , Schatzberg Alan F.
Published: July 2009

Objective: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. Method: 276 patients with major depressive disorder (MDD) were treated with sertraline (150–200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. Results: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. Conclusion: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials.
Orphan Nuclear Receptor Rev-erb Alpha Gene (NR1D1) and Fluvoxamine Response in Major Depressive Disorder in the Japanese Population
Authors: Kishi Taro , Kitajima Tsuyoshi , Ikeda Masashi , Yamanouchi Yoshio , Kinoshita Yoko , Kawashima Kunihiro , Okochi Tomo , Ozaki Norio , Iwata Nakao
Published: July 2009

Background: Sleep-wake disturbance, frequently observed in major depressive disorder (MDD), negatively influences clinical status. Treatment with antidepressants also reportedly affects circadian rhythms. In a recent in vitro study, the nuclear receptor Rev-erbα was reported to be related to circadian rhythms, and was shown to be involved in the biological action of lithium therapy. Therefore, we examined the association between the orphan nuclear receptor Rev-erbα gene (NR1D1) and the efficacy of fluvoxamine treatment in 118 Japanese patients with major depressive disorder. Methods: The scores of the MDD patients in this study on the 17 items of the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-D) were 12 or higher. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks and clinical remission as a SIGH-D score of less than 7 at 8 weeks. We selected 3 ‘tagging SNPs’ in NR1D1 for the following association analysis. Results: We did not detect a significant association between NR1D1 and the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis or haplotype-wise analysis. Conclusion: Our results suggest that NR1D1 does not play a major role in the therapeutic response to fluvoxamine in Japanese MDD patients. However, because our sample was small, a replication study using another population and a larger sample will be required for conclusive results.
Incidence, Case-Fatalities and 10-Year Survival of Subarachnoid Hemorrhage in a Population-Based Registry
Authors: Sacco Simona , Totaro Rocco , Toni Danilo , Marini Carmine , Cerone Davide , Carolei Antonio
Published: July 2009

Objective: To evaluate incidence, case fatalities and prognosis of subarachnoid hemorrhage (SAH). Subjects and Methods: Prospective population-based registry (1994–1998) including patients with a first-ever stroke followed up to 10 years. Results: In a 5-year period we included 118 patients (55 men and 63 women; mean age ± SD 60.7 ± 15.9 years) with an SAH. The crude annual incidence rate was 7.93 cases per 100,000 inhabitants (95% CI 6.46–9.63), 7.60 per 100,000 when standardized to the 2006 European population and 5.27 per 100,000 when standardized to the 2005 world population. The 7-day case-fatality rate was 16.1% (95% CI 9.5–22.7), 30-day case-fatality rate was 34.7% (95% CI 21.2–43.3), and 1-year case-fatality rate was 44.9% (95% CI 35.9–53.9). At the end of the 1-year follow-up, 53 patients (44.9%) had a good recovery [modified Rankin scale (mRS) 0–2] and 12 (10.2%) had a severe disability (mRS 3–5). The 10-year survival rate was 46.4% (95% CI 36.0–57.8). Conclusion: In our district, the SAH incidence rate was similar to what is reported in most European countries. Since more than half of the patients with SAH remained severely disabled or died, results from our population-based study strongly support the notion that the most appropriate treatments should be made available for all patients in comprehensive centers and the call for an urgent implementation of telemedicine in the rural areas of our district.
Elevated Troponin after Stroke: A Systematic Review
Authors: Kerr Gillian , Ray Gautamananda , Wu Olivia , Stott David J. , Langhorne Peter
Published: July 2009

Background: Troponin levels are elevated in some acute stroke patients, but the clinical significance of this is unclear. Methods: We conducted a systematic review of studies measuring troponin within 7 days of symptom onset in acute stroke patients. Results: We identified 15 studies (2,901 patients). Overall 18.1% (95% CI 13.6–22.6) had a positive troponin level. These patients were more likely to have electrocardiogram (ECG) changes suggestive of myocardial ischemia (OR 3.0; 95% CI 1.5–6.2), and there was an independent association with death (OR 2.9; 95% CI 1.7–4.8). Conclusion: Elevated troponin level after acute stroke is common and is associated with ECG changes suggestive of myocardial ischemia and increased risk of death.
Timing of Relapse and Outcome after Curative Resection for Colorectal Cancer: A Japanese Multicenter Study
Authors: Kobayashi Hirotoshi , Mochizuki Hidetaka , Morita Takayuki , Kotake Kenjiro , Teramoto Tatsuo , Kameoka Shingo , Saito Yukio , Takahashi Keiichi , Hase Kazuo , Ohya Masatoshi , Maeda Koutarou , Hirai Takashi , Kameyama Masao , Shirouzu Kazuo , Sugihara Kenichi
Published: July 2009

Background: The aim of this multicenter study was to clarify the influence of timing of relapse after curative resection for colorectal cancer on prognosis. Methods: We enrolled 5,230 consecutive patients who underwent curative resection for colorectal cancer at 14 hospitals from 1991 to 1996. All patients were intensively followed up. Time to relapse (TR) was classified into three groups as follows: group A, TR ≤1 year; group B, TR >1 year and ≤3 years, and group C, TR >3 years. The prognoses after relapse were compared among the three groups. Results: Of the 5,230 patients, 906 experienced relapse (17.3%). The curative resection rates for recurrent tumors were 35.2% in group A, 46.6% in group B, and 45.1% in group C (p = 0.0045). There were significant differences in the prognoses after relapse among the three TR groups in patients with relapse to the liver (p = 0.0175) and in those with local relapses (p = 0.0021), but not in those with pulmonary or anastomotic recurrence. There were no differences in prognoses after relapse in any recurrence site among the three groups in patients who underwent curative resection for relapse. Conclusion: If patients can undergo curative resection for relapse, they receive a survival benefit regardless of the timing of relapse.
Dimethyl Sulfoxide-Induced Toxicity in Cord Blood Stem Cell Transplantation: Report of Three Cases and Review of the Literature
Authors: Ruiz-Delgado Guillermo J. , Mancías-Guerra Consuelo , Tamez-Gómez Edna L. , Rodríguez-Romo Laura N. , López-Otero Avril , Hernández-Arizpe Ana , Gómez-Almaguer David , Ruiz-Argüelles Guillermo J.
Published: July 2009

Umbilical cord blood transplantation using nonmyeloablative conditioning is currently considered by many as a valid potential alternative for any patient who requires an unrelated donor allograft and who is without a suitably matched and readily available volunteer. Dimethyl sulfoxide (DMSO) has been used for years as a cryoprotectant agent; it acts by penetrating the cell and binding water molecules and it has been described as harmless for the individual who receives it in limited amounts. In this paper, we describe 3 cases of DMSO-induced toxicities and briefly review the most common adverse reactions of the DMSO when used as a cryopreservation agent for the long-term storage of cord blood cells. Two of the 3 cases had a dismal prognosis. A brief review of the literature is presented.
Midlife Crisis: A Debate
Authors: Freund Alexandra M. , Ritter Johannes O.
Published: July 2009

Without doubt, the midlife crisis is the most popular concept describing middle adulthood. Facing the limitation of the time until death, men in particular are believed to pause from actively pursuing their goals and review their achievements, take stock of what they have and have not yet accomplished, at times taking drastic measures to fulfill their dreams. This paper critically discusses the concept of a midlife crisis and the relevant empirical evidence, presenting arguments for and against a strict, a moderate, and a lenient conceptualization of the midlife crisis. Although a strict and even moderate definition of the midlife crisis does not seem tenable on empirical and theoretical grounds, a lenient conceptualization has the potential to stimulate new research directions exemplifying processes of the interaction of social expectations on the one hand and personal goals on the other, and their importance for developmental regulation.
Secondary Hyperparathyroidism Is Associated with Increased Risk of Hospitalization or Death in Elderly Adults Living in a Geriatric Institution
Authors: Premaor Melissa Orlandin , Scalco Rosana , Souza da Silva Marília Judith , Weber Furlanetto Tania
Published: July 2009

Background: The presence of secondary hyperparathyroidism is very frequent in the elderly population living in geriatric institutions. It has been associated with an increased mortality rate in previous studies. Objectives: To evaluate the association of secondary hyperparathyroidism with mortality or hospitalization or both (combined outcome) during a 6-month period in individuals living in geriatric institutions. Methods: A cohort of 100 individuals aged between 65 and 102 years living in geriatric institutions in the city of Porto Alegre, Brazil, was prospectively studied. Serum levels of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), albumin, total calcium, phosphorus, magnesium, creatinine and alkaline phosphatase were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault equation. Secondary hyperparathyroidism was defined as serum PTH levels higher than 48 pg/ml and normal or reduced serum calcium levels. The deaths were verified by means of death certificates and hospitalization by the discharge summaries provided by the Brazilian health system hospitals. Results: Fifty-eight percent of the individuals had secondary hyperparathyroidism, defined as serum PTH >48 pg/ml and normal or low serum calcium. Mean serum 25(OH)D levels were 12.5 ± 8 ng/ml. The odds ratio of an individual with secondary hyperparathyroidism to die, to be hospitalized or to have the combined outcome within 6 months was 6.6 [confidence interval (CI) 95% 0.8–54.6; p = 0.07], 10.7 (CI 95% 1.3–85.9; p = 0.007) and 5.20 (CI 95% 1.10–27.7; p = 0.04), respectively. Secondary hyperparathyroidism and body mass index were independently associated with the combined outcome, after correction for the GFR and 25(OH)D. Conclusion: Secondary hyperparathyroidism could be an important prognostic factor for individuals living in geriatric institutions.
Regulation of Aeroallergen Immunity by the Innate Immune System: Laboratory Evidence for a New Paradigm
Authors: Horner Anthony A.
Published: July 2009

Over the last decade, it has become increasingly clear that innate responses to microbes are mediated largely by toll-like receptors (TLRs), which recognize a diverse family of molecules produced by viruses, bacteria and fungi. This article will present evidence that TLRs also play a dominant role in innate responses to non-infectious immunostimulatory materials present in house dust extracts (HDEs) and the living environments they represent. However, our investigations challenge the commonly held view that microbial products in ambient air protect against the allergic march by promoting protective Th1 biased responses to inspired aeroallergens. Instead, all HDEs studied to date have preferentially promoted the development of Th2 biased airway hypersensitivities when used as adjuvants for intranasal (i.n.) vaccination. In contrast, daily low dose i.n. HDE delivery was found to promote the development of aeroallergen tolerance. This article will review these experimental findings as evidence to propose a new paradigm by which airborne TLR ligands and other stimulants of innate immunity may influence aeroallergen specific immunity and the genesis of allergic respiratory diseases.
A Comprehensive Review of Evidence-Based Strategies to Prevent and Treat Postoperative Ileus
Authors: Story Sara K. , Chamberlain Ronald S.
Published: July 2009

Background: Postoperative ileus (POI) is a common complication of abdominal and several other surgeries leading to increased hospital stay and healthcare costs. POI also contributes towards numerous postsurgical comorbidities including deep vein thrombosis and pneumonia. POI is characterized by bowel distention and lack of bowel sounds, flatus and bowel movements. The causative mechanism is not fully understood and may be multifactorial including disorganized electrical activity, activation of inflammatory mediators and the use of opioid analgesics. Methods: A selective review of the literature pertaining to the prevention and treatment of adynamic ileus and POI was completed. More specifically we sought to evaluate RCTs, meta-analyses, consensus statements and articles providing graded evidence-based data on POI prevention and treatment. Results: Perioperative strategies employed to prevent or limit the duration of POI include avoidance of preoperative fasting and mechanical bowel preparation, use of epidural-local anesthetics, implementation of minimally-invasive surgical techniques, and modification of pain management strategies to limit opioid administration among others. Conclusion: Though many of these strategies have proven beneficial, no single approach has demonstrated the ability to prevent or treat POI. However, when these strategies are used in combination as part of a fast-track multimodal treatment plan, there is a significant decrease in time to return of normal bowel function and a shortened hospital stay. Additional studies are needed to make specific recommendations regarding which components of fast-track protocols are most beneficial.
Short-Term Memory and Restitution During Ventricular Fibrillation in Human Hearts
Authors: Toal Satish C. , Farid Talha A. , Selvaraj Raja , Chauhan Vijay S. , Masse Stephane , Ivanov Joan , Harris Louise , Downar Eugene , Franz Michael R. , Nanthakumar Kumaraswamy
Published: July 2009

Background—

Action potential duration (APD) variation is an important determinant of wave break and reentry. The determinants of APD variability during early ventricular fibrillation (VF) in myopathic human hearts have not been studied. The objective of this study was to study the role of APD restitution and short-term cardiac memory on variation in human VF.

Methods and Results—

The study consisted of 7 patients (67�9 years old) with ejection fraction <35%. Monophasic action potentials were recorded from the right and/or left ventricular septum during VF. APD
60/90
was measured in sinus beat preceding induction of VF, and its amplitude was used to define 60%/90% repolarization in VF. The monophasic action potential upstroke (dV/dt
max
) was used to characterize local excitability. Simple linear regression showed that variability in APD
n60
was determined by APD/diastolic interval restitution (
R
2
=0.48,
P
<0.0001) and short-term memory (APD
60
n−1, n−2, n−3, n−4;
R
2
=0.55, 0.40, 0.33, and 0.27 respectively;
P
<0.001). Using multiple stepwise regression, short-term memory and restitution accounted for 62% of variance in APD
60
(
P
<0.001). Individually, memory effect had the greatest contribution to APD variability (
R
2
=0.55,
P
<0.0001).

Conclusions—

In early human VF, short-term memory and APD/diastolic interval restitution explain most of the APD variability, with memory effects predominating. This suggests that in early human VF, short-term cardiac memory may provide a novel therapeutic target to modulate progression of VF in myopathic patients.