bluuebunny/crossref_metadata_2025 huggingface dataset:
RAMAN SPECTROSCOPIC STUDY ON PREDICTION OF TREATMENT RESPONSE IN CERVICAL CANCERS
Authors: RUBINA S. , VIDYASAGAR M. S. , MURALI KRISHNA C.
Published: January 2013

Concurrent chemoradiotherapy (CCRT) is the choice of treatment for locally advanced cervical cancers; however, tumors exhibit diverse response to treatment. Early prediction of tumor response leads to individualizing treatment regimen. Response evaluation criteria in solid tumors (RECIST), the current modality of tumor response assessment, is often subjective and carried out at the first visit after treatment, which is about four months. Hence, there is a need for better predictive tool for radioresponse. Optical spectroscopic techniques, sensitive to molecular alteration, are being pursued as potential diagnostic tools. Present pilot study aims to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT, before taking up extensive in vivo studies. Ex vivo Raman spectra were acquired from biopsies collected from 11 normal (148 spectra), 16 tumor (201 spectra) and 13 complete response (151 CR spectra), one partial response (8 PR spectra) and one nonresponder (8 NR spectra) subjects. Data was analyzed using principal component linear discriminant analysis (PC-LDA) followed by leave-one-out cross-validation (LOO-CV). Findings suggest that normal tissues can be efficiently classified from both pre- and post-treated tumor biopsies, while there is an overlap between pre- and post-CCRT tumor tissues. Spectra of CR, PR and NR tissues were subjected to principal component analysis (PCA) and a tendency of classification was observed, corroborating previous studies. Thus, this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.
Effective contractile response to voltage-gated Na+ channels revealed by a channel activator
Authors: Ho W.-S. Vanessa , Davis Alison J. , Chadha Preet S. , Greenwood Iain A.
Published: January 2013

This study investigated the molecular identity and impact of enhancing voltage-gated Na+ (NaV) channels in the control of vascular tone. In rat isolated mesenteric and femoral arteries mounted for isometric tension recording, the vascular actions of the NaV channel activator veratridine were examined. NaV channel expression was probed by molecular techniques and immunocytochemistry. In mesenteric arteries, veratridine induced potent contractions (pEC50 = 5.19 ± 0.20, Emax = 12.0 ± 2.7 mN), which were inhibited by 1 μM TTX (a blocker of all NaV channel isoforms, except NaV1.5, NaV1.8, and NaV1.9), but not by selective blockers of NaV1.7 (ProTx-II, 10 nM) or NaV1.8 (A-80347, 1 μM) channels. The responses were insensitive to endothelium removal but were partly (∼60%) reduced by chemical destruction of sympathetic nerves by 6-hydroxydopamine (2 mM) or antagonism at the α1-adrenoceptor by prazosin (1 μM). KB-R7943, a blocker of the reverse mode of the Na+/Ca2+ exchanger (3 μM), inhibited veratridine contractions in the absence or presence of prazosin. T16Ainh-A01, a Ca2+-activated Cl− channel blocker (10 μM), also inhibited the prazosin-resistant contraction to veratridine. NaV channel immunoreactivity was detected in freshly isolated mesenteric myocytes, with apparent colocalization with the Na+/Ca2+ exchanger. Veratridine induced similar contractile effects in the femoral artery, and mRNA transcripts for NaV1.2 and NaV1.3 channels were evident in both vessel types. We conclude that, in addition to sympathetic nerves, NaV channels are expressed in vascular myocytes, where they are functionally coupled to the reverse mode of Na+/Ca2+ exchanger and subsequent activation of Ca2+-activated Cl− channels, causing contraction. The TTX-sensitive NaV1.2 and NaV1.3 channels are likely involved in vascular control.
Diversity of lipid mediators in human adipose tissue depots
Authors: Clària Joan , Nguyen Binh T. , Madenci Arin L. , Ozaki C. Keith , Serhan Charles N.
Published: January 2013

Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The “classic” eicosanoids prostaglandin (PG) E2, PGD2, PGF2α, leukotriene (LT) B4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2α differed significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE2. In this tissue, proresolving mediators RvD2 and LXA4 were identified in lower levels than the proinflammatory LTB4. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD.
Genetic mutation of recombination activating gene 1 in Dahl salt-sensitive rats attenuates hypertension and renal damage
Authors: Mattson David L. , Lund Hayley , Guo Chuanling , Rudemiller Nathan , Geurts Aron M. , Jacob Howard
Published: January 2013

Hypertension and renal damage in Dahl SS rats are associated with increased infiltrating immune cells in the kidney. To examine the role of infiltrating immune cells in this disease process, a zinc finger nuclease targeting bases 672–706 of recombination-activating gene 1 (Rag1) was injected into the pronucleus of Dahl SS (SS/JrHsdMcwi) strain embryos and implanted in pseudopregnant females. This strategy yielded a rat strain with a 13-base frame-shift mutation in the target region of Rag1 and a deletion of immunoreactive Rag1 protein in the thymus. Flow cytometry demonstrated that the Rag1-null mutant rats have a significant reduction in T and B lymphocytes in the circulation and spleen. Studies were performed on SS and Rag1-null rats fed a 4.0% NaCl diet for 3 wk. The infiltration of T cells into the kidney following high-salt intake was significantly blunted in the Rag1-null rats (1.7 ± 0.6 × 105 cells/kidney) compared with the Dahl SS (5.6 ± 0.9 × 105 cells/kidney). Accompanying the reduction in infiltration of immune cells in the kidney, mean arterial blood pressure and urinary albumin excretion rate were significantly lower in Rag1-null mutants (158 ± 3 mmHg and 60 ± 16 mg/day, respectively) than in SS rats (180 ± 11 mmHg and 251 ± 37 mg/day). Finally, a histological analysis revealed that the glomerular and tubular damage in the kidneys of the SS rats fed a high-salt diet was also attenuated in the Rag1 mutants. These studies demonstrate the importance of renal infiltration of immune cells in the pathogenesis of hypertension and renal damage in Dahl SS rats.
Role of cardiac natriuretic peptides in seawater adaptation of medaka embryos as revealed by loss-of-function analysis
Authors: Miyanishi Hiroshi , Okubo Kataaki , Kaneko Toyoji , Takei Yoshio
Published: January 2013

Cardiac natriuretic peptides (atrial natriuretic peptide, ANP; b-type natriuretic peptide, BNP; ventricular natriuretic peptide, VNP) and their direct ancestor C-type natriuretic peptide 3 (CNP3) exert potent osmoregulatory actions in fish. However, very little is known about their roles in embryonic osmoregulation. In this study, we performed loss-of-function analysis using euryhaline medaka ( Oryzias latipes), which has lost ANP and VNP during evolution and thus possesses only BNP and CNP3. We found that the maintenance of whole-body osmolality in seawater embryos was impaired by the knockdown of BNP+OLGC7 (BNP receptor) or CNP3 alone from 1 day postfertilization, and the CNP3 knockdown was accompanied by greater water loss. The impaired osmoregulation in the knockdown embryos was not due to the suppressed expression of major transporters for NaCl excretion via ionocytes or of key enzyme genes for metabolic water production, but to the impaired blood circulation to the yolk-sac membrane caused by abnormal heart development. We detected a strong positive correlation between impaired blood circulation and increased body fluid osmolality and pharmacological blockade of blood flow increased body fluid osmolality in seawater embryos. We also found that the exaggerated water loss in CNP3 knockdown embryos is related to the failure to suppress aquaporin (AQP3, AQP4, and AQP9) gene expression. These results show that CNP3 decrease water permeability of body surfaces and that both BNP and CNP3 ensure sufficient blood flow to the yolk-sac membrane for efficient salt excretion by ionocytes and sufficient water production by yolk metabolism to promote seawater adaptation during early development in medaka.
The tight junction protein claudin-b regulates epithelial permeability and sodium handling in larval zebrafish,Danio rerio
Authors: Kwong Raymond W. M. , Perry Steve F.
Published: January 2013

The functional role of the tight junction protein claudin-b in larval zebrafish ( Danio rerio) was investigated. We showed that claudin-b protein is expressed at epithelial cell-cell contacts on the skin. Translational gene knockdown of claudin-b protein expression caused developmental defects, including edema in the pericardial cavity and yolk sac. Claudin-b morphants exhibited an increase in epithelial permeability to the paracellular marker polyethylene glycol (PEG-4000) and fluorescein isothiocyanate-dextran (FD-4). Accumulation of FD-4 was confined mainly to the yolk sac and pericardial cavity in the claudin-b morphants, suggesting these regions became particularly leaky in the absence of claudin-b expression. Additionally, Na+efflux was substantially increased in the claudin-b morphants, which contributed to a significant reduction in whole-body Na+levels. These results indicate that claudin-b normally acts as a paracellular barrier to Na+. Nevertheless, the elevated loss of Na+in the morphants was compensated by an increase in Na+uptake. Notably, we observed that the increased Na+uptake in the morphants was attenuated in the presence of the selective Na+/Cl−-cotransporter (NCC) inhibitor metolazone, or during exposure to Cl−-free water. These results suggested that the increased Na+uptake in the morphants was, at least in part, mediated by NCC. Furthermore, treatment with an H+-ATPase inhibitor bafilomycin A1 was found to reduce Na+uptake in the morphants, suggesting that H+-ATPase activity was essential to provide a driving force for Na+uptake. Overall, the results suggest that claudin-b plays an important role in regulating epithelial permeability and Na+handling in zebrafish.
Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla
Authors: Pannabecker Thomas L.
Published: January 2013

Comparative studies of renal structure and function have potential to provide insights into the urine-concentrating mechanism of the mammalian kidney. This review focuses on the tubular transport pathways for water and urea that play key roles in fluid and solute movements between various compartments of the rodent renal inner medulla. Information on aquaporin water channel and urea transporter expression has increased our understanding of functional segmentation of medullary thin limbs of Henle's loops, collecting ducts, and vasa recta. A more complete understanding of membrane transporters and medullary architecture has identified new and potentially significant interactions between these structures and the interstitium. These interactions are now being introduced into our concept of how the inner medullary urine-concentrating mechanism works. A variety of regulatory pathways lead directly or indirectly to variable patterns of fluid and solute movements among the interstitial and tissue compartments. Animals with the ability to produce highly concentrated urine, such as desert species, are considered to exemplify tubular structure and function that optimize urine concentration. These species may provide unique insights into the urine-concentrating process.1
Reduced c-Fos expression in medullary catecholaminergic neurons in rats 20 h after exposure to chronic intermittent hypoxia
Authors: Herr Kate Benincasa , Stettner Georg M. , Kubin Leszek
Published: January 2013

Persons affected by obstructive sleep apnea (OSA) have increased arterial blood pressure and elevated activity in upper airway muscles. Many cardiorespiratory features of OSA have been reproduced in rodents subjected to chronic-intermittent hypoxia (CIH). We previously reported that, following exposure to CIH, rats have increased noradrenergic terminal density in brain stem sensory and motor nuclei and upregulated expression of the excitatory α1-adrenergic receptors in the hypoglossal motor nucleus. This suggested that CIH may enhance central catecholaminergic transmission. We now quantified c-Fos expression in different groups of pontomedullary catecholaminergic neurons as an indirect way of assessing their baseline activity in rats subjected to CIH or sham treatment (7 AM-5 PM daily for 35 days). One day after the last CIH exposure, the rats were gently kept awake for 2.5 h and then were anesthetized and perfused, and their pontomedullary brain sections were subjected to dopamine β-hydroxylase (DBH) and c-Fos immunohistochemistry. DBH-positive cells were counted in the A1/C1, A2/C2, A5, subcoeruleus (sub-C) and A7 groups of catecholaminergic neurons, and the percentages of those expressing c-Fos were determined. We found that fewer DBH cells expressed c-Fos in CIH- than in sham-treated rats in the medulla (significant in the A1 group). In the pons (rostral A5, sub-C, and A7), c-Fos expression did not differ between the CIH- and sham-treated animals. We suggest that, when measured 20 h after the last CIH exposure, catecholaminergic transmission is enhanced through terminal sprouting and receptor upregulation rather than through increased baseline activity in pontomedullary catecholaminergic neurons.
Impaired pressure natriuresis resulting in salt-sensitive hypertension is caused by tubulointerstitial immune cell infiltration in the kidney
Authors: Franco Martha , Tapia Edilia , Bautista Rocio , Pacheco Ursino , Santamaria Jose , Quiroz Yasmir , Johnson Richard J. , Rodriguez-Iturbe Bernardo
Published: January 2013

Immune cell infiltration of the kidney is a constant feature in salt-sensitive hypertension (SSHTN). We evaluated the relationship between the renal inflammation and pressure natriuresis in the model of SSHTN that results from transient oral administration of Nω-nitro-l-arginine methyl ester (l-NAME). Pressure natriuresis was determined in Wistar rats that received 4 wk of a high-salt (4% NaCl) diet, starting 1 wk after stopping l-NAME, which was administered alone (SSHTN group, n = 17) or in association with mycophenolate mofetil (MMF; MMF group, n = 15). The administration of MMF in association with l-NAME is known to prevent the subsequent development of SSHTN. Control groups received a high ( n = 12)- and normal (0.4%)-salt diet ( n = 20). Rats with SSHTN had increased expression of inflammatory cytokines and oxidative stress. The severity of hypertension correlated directly ( P < 0.0001) with the number of tubulointerstitial immune cells and angiotensin II-expressing cells. Pressure natriuresis was studied at renal arterial pressures (RAPs) of 90, 110, 130, and 150 mmHg. Glomerular filtration rate was similar and stable in all groups, and renal blood flow was decreased in the SSHTN group. Significantly decreased natriuresis ( P < 0.05) was found in the SSHTN group at RAPs of 130 and 150 mmHg, and there was an inverse correlation ( P < 0.01) between the urinary sodium excretion and the number of tubulointerstitial inflammatory cells (lymphocytes and macrophages) and cells expressing angiotensin II. We conclude that tubulointerstitial inflammation plays a key role in the impairment of pressure natriuresis that results in salt-dependent hypertension in this experimental model.
Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model
Authors: Wang Diping , Warner Gina M. , Yin Ping , Knudsen Bruce E. , Cheng Jingfei , Butters Kim A. , Lien Karen R. , Gray Catherine E. , Garovic Vesna D. , Lerman Lilach O. , Textor Stephen C. , Nath Karl A. , Simari Robert D. , Grande Joseph P.
Published: January 2013

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.
Deficits in anticipatory inhibition of postural muscle activity associated with load release while standing in individuals with spastic diplegic cerebral palsy
Authors: Tomita Hidehito , Fukaya Yoshiki , Totsuka Kenji , Tsukahara Yuri
Published: January 2013

This study aimed to determine whether individuals with spastic diplegic cerebral palsy (SDCP) have deficits in anticipatory inhibition of postural muscle activity. Nine individuals with SDCP (SDCP group, 3 female and 6 male, 13–24 yr of age) and nine age- and sex-matched individuals without disability (control group) participated in this study. Participants stood on a force platform, which was used to measure the position of the center of pressure (CoP), while holding a light or heavy load in front of their bodies. They then released the load by abducting both shoulders. Surface electromyograms were recorded from the rectus abdominis, erector spinae (ES), rectus femoris (RF), medial hamstring (MH), tibialis anterior (TA), and gastrocnemius (GcM) muscles. In the control group, anticipatory inhibition before load release and load-related modulation of the inhibition were observed in all the dorsal muscles recorded (ES, MH, and GcM). In the SDCP group, similar results were obtained in the trunk muscle (ES) but not in the lower limb muscles (MH and GcM), although individual differences were seen, especially in MH. Anticipatory activation of the ventral lower limb muscles (RF and TA) and load-related modulation of the activation were observed in both participant groups. CoP path length during load release was longer in the SDCP group than in the control group. The present findings suggest that individuals with SDCP exhibit deficits in anticipatory inhibition of postural muscles at the dorsal part of the lower limbs, which is likely to result in a larger disturbance of postural equilibrium.
Kinetic adaptation during locomotion on a split-belt treadmill
Authors: Mawase Firas , Haizler Tamar , Bar-Haim Simona , Karniel Amir
Published: January 2013

It has been suggested that a feedforward control mechanism drives the adaptation of the spatial and temporal interlimb locomotion variables. However, the internal representation of limb kinetics during split-belt locomotion has not yet been studied. In hand movements, it has been suggested that kinetic and kinematic parameters are controlled by separate neural processes; therefore, it is possible that separate neural processes are responsible for kinetic and kinematic locomotion parameters. In the present study, we assessed the adaptation of the limb kinetics by analyzing the ground reaction forces (GRFs) as well as the center of pressure (COP) during adaptation to speed perturbation, using a split-belt treadmill with an integrated force plate. We found that both the GRF of each leg at initial contact and the COP changed gradually and showed motor aftereffects during early postadaptation, suggesting the use of a feedforward predictive mechanism. However, the GRF of each leg in the single-support period used a feedback control mechanism. It changed rapidly during the adaptation phase and showed no motor aftereffect when the speed perturbation was removed. Finally, we found that the motor adaptation of the GRF and the COP are mediated by a dual-rate process. Our results suggest two important contributions to neural control of locomotion. First, different control mechanisms are responsible for forces at single- and double-support periods, as previously reported for kinematic variables. Second, our results suggest that motor adaptation during split-belt locomotion is mediated by fast and slow adaptation processes.
Parameterized phase response curves for characterizing neuronal behaviors under transient conditions
Authors: Miranda-Domínguez Óscar , Netoff Theoden I.
Published: January 2013

Phase response curves (PRCs) are a simple model of how a neuron's spike time is affected by synaptic inputs. PRCs are useful in predicting how networks of neurons behave when connected. One challenge in estimating a neuron's PRCs experimentally is that many neurons do not have stationary firing rates. In this article we introduce a new method to estimate PRCs as a function of firing rate of the neuron. We call the resulting model a parameterized PRC (pPRC). Experimentally, we perturb the neuron applying a current with two parts: 1) a current held constant between spikes but changed at the onset of a spike, used to make the neuron fire at different rates, and 2) a pulse to emulate a synaptic input. A model of the applied constant current and the history is made to predict the interspike interval (ISI). A second model is then made to fit the modulation of the spike time from the expected ISI by the pulsatile stimulus. A polynomial with two independent variables, the stimulus phase and the expected ISI, is used to model the pPRC. The pPRC is validated in a computational model and applied to pyramidal neurons from the CA1 region of the hippocampal slices from rat. The pPRC can be used to model the effect of changing firing rates on network synchrony. It can also be used to characterize the effects of neuromodulators and genetic mutations (among other manipulations) on network synchrony. It can also easily be extended to account for more variables.
Transient shifts in frontal and parietal circuits scale with enhanced visual feedback and changes in force variability and error
Authors: Poon Cynthia , Coombes Stephen A. , Corcos Daniel M. , Christou Evangelos A. , Vaillancourt David E.
Published: January 2013

When subjects perform a learned motor task with increased visual gain, error and variability are reduced. Neuroimaging studies have identified a corresponding increase in activity in parietal cortex, premotor cortex, primary motor cortex, and extrastriate visual cortex. Much less is understood about the neural processes that underlie the immediate transition from low to high visual gain within a trial. This study used 128-channel electroencephalography to measure cortical activity during a visually guided precision grip task, in which the gain of the visual display was changed during the task. Force variability during the transition from low to high visual gain was characterized by an inverted U-shape, whereas force error decreased from low to high gain. Source analysis identified cortical activity in the same structures previously identified using functional magnetic resonance imaging. Source analysis also identified a time-varying shift in the strongest source activity. Superior regions of the motor and parietal cortex had stronger source activity from 300 to 600 ms after the transition, whereas inferior regions of the extrastriate visual cortex had stronger source activity from 500 to 700 ms after the transition. Force variability and electrical activity were linearly related, with a positive relation in the parietal cortex and a negative relation in the frontal cortex. Force error was nonlinearly related to electrical activity in the parietal cortex and frontal cortex by a quadratic function. This is the first evidence that force variability and force error are systematically related to a time-varying shift in cortical activity in frontal and parietal cortex in response to enhanced visual gain.
Electrical tuning and transduction in short hair cells of the chicken auditory papilla
Authors: Tan Xiaodong , Beurg Maryline , Hackney Carole , Mahendrasingam Shanthini , Fettiplace Robert
Published: January 2013

The avian auditory papilla contains two classes of sensory receptor, tall hair cells (THCs) and short hair cells (SHCs), the latter analogous to mammalian outer hair cells with large efferent but sparse afferent innervation. Little is known about the tuning, transduction, or electrical properties of SHCs. To address this problem, we made patch-clamp recordings from hair cells in an isolated chicken basilar papilla preparation at 33°C. We found that SHCs are electrically tuned by a Ca2+-activated K+current, their resonant frequency varying along the papilla in tandem with that of the THCs, which also exhibit electrical tuning. The tonotopic map for THCs was similar to maps previously described from auditory nerve fiber measurements. SHCs also possess an A-type K+current, but electrical tuning was observed only at resting potentials positive to −45 mV, where the A current is inactivated. We predict that the resting potential in vivo is approximately −40 mV, depolarized by a standing inward current through mechanotransducer (MT) channels having a resting open probability of ∼0.26. The resting open probability stems from a low endolymphatic Ca2+concentration (0.24 mM) and a high intracellular mobile Ca2+buffer concentration, estimated from perforated-patch recordings as equivalent to 0.5 mM BAPTA. The high buffer concentration was confirmed by quantifying parvalbumin-3 and calbindin D-28K with calibrated postembedding immunogold labeling, demonstrating >1 mM calcium-binding sites. Both proteins displayed an apex-to-base gradient matching that in the MT current amplitude, which increased exponentially along the papilla. Stereociliary bundles also labeled heavily with antibodies against the Ca2+pump isoform PMCA2a.
Mechanisms of responsibility assignment during redundant reaching movements
Authors: Reichenbach Alexandra , Costello Angela , Zatka-Haas Peter , Diedrichsen Jörn
Published: January 2013

When the two hands act together to achieve a goal, the redundancy of the system makes it necessary to distribute the responsibility for error corrections across the two hands. In an experiment in which participants control a single cursor with the movements of both hands, we show that right-handed individuals correct for movement errors more with their nondominant left hand than with their right hand, even though the dominant right hand corrects the same errors more quickly and efficiently when each hand acts in isolation. By measuring the responses to rapid cursor and target displacements using force channels, we demonstrate that this shift is due to a modulation of the feedback gains of each hand rather than to a shift in the onset of the corrective response. We also show that the shift toward left-hand corrections is more pronounced for errors that lead to adaptation (cursor displacements) than for perturbations that do not (target displacements). This finding provides some support for the idea that the motor system assigns the correction to the most likely source of the error to induce learning and to optimize future performance. Finally, we find that the relative strength of the feedback corrections in the redundant task correlates positively with those found for the nonredundant tasks. Thus the process of responsibility assignment modulates the processes that normally determine the gains of feedback correction rather than completely overwriting them.
The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers
Authors: Nasyuhana Sani Yanti , Sheau Chin Lim , Luen Hui Lim , Mohd Redhuan Shah Edwin Nur Elyana Yazmin , Teck Hwa Goh , Serebruany Victor L. , Kah Hay Yuen
Published: January 2013

Background. TheCYP2C19*2allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whetherCYP2C19*2alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers.Methods. Ninety volunteers were genotyped forCYP2C19*2andCYP2C19*3alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely,CYP2C19*1/*1(n=17),CYP2C19*1/*2(n=21),andCYP2C19*2/*2(n=7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230.Results. Following clopidogrel intake,CYP2C19*2/*2carriers had a significantly higher mean PRU compared to theCYP2C19*1/*2andCYP2C19*1/*1(291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU,P<0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 wereCYP2C19*1/*1, 11 wereCYP2C19*1/*2, and 7 wereCYP2C19*2/*2).Conclusion. In healthy Malaysian volunteers,CYP2C19*2allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers ofCYP2C19*2/*2, but also in the carriers ofCYP2C19*1/*2andCYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy.
Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids
Authors: Estadella Débora , da Penha Oller do Nascimento Claudia M. , Oyama Lila M. , Ribeiro Eliane B. , Dâmaso Ana R. , de Piano Aline
Published: January 2013

The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.
Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer
Authors: Jorge Yvana Cristina , Mataruco Mayra Mioto , Araújo Leandro Pires , Rossi Ana Flávia Teixeira , de Oliveira Juliana Garcia , Valsechi Marina Curado , Caetano Alaor , Miyazaki Kenji , Fazzio Célia Sebastiana de Jesus , Thomé Jorge Alberto , Rahal Paula , Oliani Sonia Maria , Silva Ana Elizabete
Published: January 2013

Objective. The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1) and galectin-1 (LGALS1/Gal-1) in an inflammatory gastric lesion as chronic gastritis (CG) and gastric adenocarcinoma (GA) and its association withH. pyloriinfection.Methods. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C) by the quantitative real-time PCR (qPCR) technique and the immunohistochemistry assay.Results. HighANXA1mRNA expression levels were observed in 90% (36/40) of CG cases (mean relative quantification RQ = 4.26 ± 2.03) and in 80% (16/20) of GA cases (mean RQ = 4.38 ± 4.77). However,LGALS1mRNA levels were high (mean RQ = 2.44 ± 3.26) in 60% (12/20) of the GA cases, while low expression was found in CG (mean RQ = 0.43±3.13;P<0.01). Normal mucosa showed modest immunoreactivity in stroma but not in epithelium, while stroma and epithelium displayed an intense immunostaining in CG and GA for both proteins.Conclusion. These results have provided evidence that galectin-1 and mainly annexin-A1 are overexpressed in both gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.
Detection and Analysis of Autoantigens Targeted by Autoantibodies in Immunorelated Pancytopenia
Authors: Liu Hui , Fu Rong , Wang Yihao , Liu Hong , Li Lijuan , Wang Honglei , Chen Jin , Yu Hong , Shao Zonghong
Published: January 2013

Previously, we described a group of patients with hemocytopenia who did not conform to diagnostic criteria of known hematological and nonhematological diseases. Most patients responded well to adrenocortical hormone and/or high-dose intravenous immunoglobulin treatment, indicating that cytopenia might be mediated by autoantibodies. Autoantibodies were detected on the membrane of various bone marrow (BM) hemopoietic cells by bone marrow mononuclear-cell-Coombs test or flow cytometric analysis. Thus, the hemocytopenia was termed “Immunorelated Pancytopenia” (IRP) to distinguish it from other pancytopenias. Autoantigens in IRP were investigated by membrane protein extraction from BM hemopoietic cells and BM supernatant from IRP patients. Autoantibody IgG was detected in the BM supernatant of 75% of patients (15/20), which was significantly higher than that in aplastic anemia, myelodysplastic syndrome, or autoimmune hemolytic anemia patients (0%) and normal healthy controls (0%) (P<0.01). Autoantigens had approximate molecular weights of 25, 30, 47.5, 60, 65, 70, and 80 kDa, some of which were further identified by mass fingerprinting. This study identified that a G-protein-coupled receptor 156 variant and chain P, a crystal structure of the cytoplasmic domain of human erythrocyte band-3 protein, were autoantigens in IRP. Further studies are needed to confirm the antigenicity of these autoantigens.
Mitochondrial-Targeted Two-Photon Fluorescent Probes for Zinc Ions,H2O2, and Thiols in Living Tissues
Authors: Kim Hwan Myung , Cho Bong Rae
Published: January 2013

Mitochondria provide the energy of the cells and are the primary site of oxygen consumption and the major source of reactive oxygen species. In mitochondria, metal ions and glutathione play vital roles in maintaining their structure and the redox environment. To understand their roles in mitochondria, it is crucial to monitor each of these chemical species in the mitochondria at the cell, tissue, and organism levels. An ideal tool for such purpose is the use of two-photon microscopy (TPM). Until recently, however, there has been no report on the two-photon (TP) probes suitable for such applications. In this paper, we summarize the mitochondria-targeted TP probes for Zn2+, H2O2, and thiols, as well as their bioimaging applications.
The Use of Strontium-90 Beta Radiotherapy as Adjuvant Treatment for Conjunctival Melanoma
Authors: Cohen Victoria M. L. , Papastefanou Vasilios P. , Liu S. , Stoker Ian , Hungerford John L.
Published: January 2013

Background/Aims. To report the safety and efficacy of strontium (Sr90) beta radiotherapy as adjuvant treatment for conjunctival melanoma.Methods. A retrospective cohort study was undertaken from 1999 to 2007 of all patients who underwent Sr90beta radiotherapy for incompletely excised conjunctival melanoma. Failure of treatment was defined as recurrence of a conjunctival melanoma at the same location following beta radiotherapy.Results. Twenty patients underwent Sr90beta radiotherapy for incompletely excised conjunctival melanoma. Median follow-up interval was 59 months (8–152). All patients had conjunctival melanoma involving the bulbar conjunctiva. Underlying diagnoses included PAM with atypia in 60% (12 of 20), PAM without atypia in 15% (3 of 20), and de novo conjunctival melanoma in 25% (5 of 20). Following Sr90beta radiotherapy, in 90% (18 out of 20) local control was achieved and visual acuity was not affected in any patient. Three patients (15%) had dry eye symptoms, episcleritis, and descemetcoele, respectively. No cataract or secondary glaucoma was reported.Conclusions. Sr90treatment is a very effective adjuvant treatment after excisional biopsy and cryotherapy for conjunctival melanoma with a local success rate of 90%. The treatment is not associated with significant side effects and visual acuity is not affected.
Analytical Solution of Non-Isothermal Diffusion-Reaction Processes and Effectiveness Factors
Authors: Ananthaswamy Vembu , Rajendran Lakshmanan
Published: January 2013

The mathematical modeling of nonlinear boundary value problems in catalytically chemical reactor is discussed. In this paper, we obtain the approximate analytical solution and the effectiveness factors for the evolution of single-step transformations under non-isothermal conditions using homotopy perturbation method. We have applied it to many reaction models and obtained very simple analytical expressions for the shape of the corresponding transformation rate peaks. These analytical solutions represent a significant simplification of the system’s description allowing easy curve fitting to experiment. The accuracy achieved with our method is checked against several reaction models and numerical results. A satisfactory agreement is noted.
A Literature Synthesis Indicates Very Low Quality, but Consistent Evidence of Improvements in Function after Surgical Interventions for Primary Osteoarthritis of the Elbow
Authors: Vincent Joshua I. , Vandervoort Anthony A. , MacDermid Joy C.
Published: January 2013

Background. Primary osteoarthritis of the elbow is a debilitating disease with an overall incidence of about 2%. Pain and reduced motion (ROM) lead to disability and loss of functional independence.Purpose. To critically review the literature on patient-related important functional outcomes (pain, ROMs and functional recovery) after surgery for primary OA of the elbow, utilizing the 2011 OCEBM levels of evidence.Design. A literature synthesis.Results. Twenty-six articles satisfied the inclusion and exclusion criteria; 25 of the studies were at level IV evidence, and 1 at level III. All three surgical techniques led to improvement in pain, ROM, and functional recovery in the short- and medium-term follow-up. Long-term follow-up results, available only for open joint debridement, showed recurrence of osteoarthritic signs on X-ray with minimal loss of motion. Recently, there seems to be an increased focus on arthroscopic debridement.Conclusion. The quality of research addressing surgical interventions is very low, including total elbow arthroplasty (TEA). However, the evidence concurs that open and arthroscopic joint debridement can improve function in patients with moderate-to-severe OA of the elbow. TEA is reserved for treating severe joint destruction, mostly for elderly individuals with low physical demands when other intervention options have failed.
A Newton-Type Algorithm for Solving Problems of Search Theory
Authors: Zhang Liping
Published: January 2013

In the survey of the continuous nonlinear resource allocation problem, Patriksson pointed out that Newton-type algorithms have not been proposed for solving the problem of search theory in the theoretical perspective. In this paper, we propose a Newton-type algorithm to solve the problem. We prove that the proposed algorithm has global and superlinear convergence. Some numerical results indicate that the proposed algorithm is promising.
Association between Lifestyle Factors and Metabolic Syndrome among African Americans in the United States
Authors: Bhanushali Chintan J. , Kumar Krishna , Wutoh Anthony K. , Karavatas Spiridon , Habib Muhammad J. , Daniel Marlon , Lee Euni
Published: January 2013

Background. Although there is a reported association between lifestyle factors and metabolic syndrome, very few studies have used national level data restricted to the African Americans (AAs) in the United States (US).Methods. A cross-sectional evaluation was conducted using the National Health and Nutrition Examination Survey from 1999 to 2006 including men and nonpregnant women of 20 years or older. Multiple logistic regression models were constructed to evaluate the association between lifestyle factors and metabolic syndrome.Results. AA women had a higher prevalence of metabolic syndrome (39.43%) than AA men (26.77%). After adjusting for sociodemographic factors, no significant association was found between metabolic syndrome and lifestyle factors including alcohol drinking, cigarette smoking, and physical activity. Age and marital status were significant predictors for metabolic syndrome. With increase in age, both AA men and AA women were more likely to have metabolic syndrome (AA men:ORadj=1.05, 95% CI 1.04–1.06, AA women:ORadj=1.06, 95% CI 1.04–1.07). Single AA women were less likely to have metabolic syndrome than married women (ORadj=0.66, 95% CI 0.43–0.99).Conclusion. Lifestyle factors had no significant association with metabolic syndrome but age and marital status were strong predictors for metabolic syndrome in AAs in the US.
Cerebral Vasospasm Pharmacological Treatment: An Update
Authors: Siasios Ioannis , Kapsalaki Eftychia Z. , Fountas Kostas N.
Published: January 2013

Aneurysmal subarachnoid hemorrhage- (aSAH-) associated vasospasm constitutes a clinicopathological entity, in which reversible vasculopathy, impaired autoregulatory function, and hypovolemia take place, and lead to the reduction of cerebral perfusion and finally ischemia. Cerebral vasospasm begins most often on the third day after the ictal event and reaches the maximum on the 5th–7th postictal days. Several therapeutic modalities have been employed for preventing or reversing cerebral vasospasm. Triple “H” therapy, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators, administration of substances like magnesium sulfate, statins, fasudil hydrochloride, erythropoietin, endothelin-1 antagonists, nitric oxide progenitors, and sildenafil, are some of the therapeutic protocols, which are currently employed for managing patients with aSAH. Intense pathophysiological mechanism research has led to the identification of various mediators of cerebral vasospasm, such as endothelium-derived, vascular smooth muscle-derived, proinflammatory mediators, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Oral, intravenous, or intra-arterial administration of antagonists of these mediators has been suggested for treating patients suffering a-SAH vasospam. In our current study, we attempt to summate all the available pharmacological treatment modalities for managing vasospasm.
A Systematic Review of Ethanol and Fomepizole Use in Toxic Alcohol Ingestions
Authors: Beatty Lorri , Green Robert , Magee Kirk , Zed Peter
Published: January 2013

Objectives. The optimal antidote for the treatment of ethylene glycol or methanol intoxication is not known. The objective of this systematic review is to describe all available data on the use of ethanol and fomepizole for methanol and ethylene glycol intoxication.Data Source. A systematic search of MEDLINE and EMBASE was conducted.Study Selection. Published studies involving the use of ethanol or fomepizole, or both, in adults who presented within 72 hours of toxic alcohol ingestion were included. Our search yielded a total of 145 studies for our analysis. There were no randomized controlled trials, and no head-to-head trials.Data Extraction. Variables were evaluated for all publications by one independent author using a standardized data collection form.Data Synthesis. 897 patients with toxic alcohol ingestion were identified. 720 (80.3%) were treated with ethanol (505 Me, 215 EG), 146 (16.3%) with fomepizole (81 Me, 65 EG), and 33 (3.7%) with both antidotes (18 Me, 15 EG). Mortality in patients treated with ethanol was 21.8% for Me and 18.1% for EG. In those administered fomepizole, mortality was 17.1% for Me and 4.1% for EG. Adverse events were uncommon.Conclusion. The data supporting the use of one antidote is inconclusive. Further investigation is warranted.
Medication Errors in a Swiss Cardiovascular Surgery Department: A Cross-Sectional Study Based on a Novel Medication Error Report Method
Authors: Küng Kaspar , Carrel Thierry , Wittwer Brigitte , Engberg Sandra , Zimmermann Natalie , Schwendimann René
Published: January 2013

The purpose of this study was (1) to determine frequency and type of medication errors (MEs), (2) to assess the number of MEs prevented by registered nurses, (3) to assess the consequences of ME for patients, and (4) to compare the number of MEs reported by a newly developed medication error self-reporting tool to the number reported by the traditional incident reporting system. We conducted a cross-sectional study on ME in the Cardiovascular Surgery Department of Bern University Hospital in Switzerland. Eligible registered nurses () involving in the medication process were included. Data on ME were collected using an investigator-developed medication error self reporting tool (MESRT) that asked about the occurrence and characteristics of ME. Registered nurses were instructed to complete a MESRT at the end of each shift even if there was no ME. All MESRTs were completed anonymously. During the one-month study period, a total of 987 MESRTs were returned. Of the 987 completed MESRTs, 288 (29%) indicated that there had been an ME. Registered nurses reported preventing 49 (5%) MEs. Overall, eight (2.8%) MEs had patient consequences. The high response rate suggests that this new method may be a very effective approach to detect, report, and describe ME in hospitals.