bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting functional motor potential in chronic stroke patients using diffusion tensor imaging
Authors: Lindenberg Robert , Zhu Lin L. , Rüber Theodor , Schlaug Gottfried
Published: April 2011

Electrophysiological and neuroimaging studies suggest that the integrity of ipsilesional and inter‐hemispheric motor circuits is important for motor recovery after stroke. However, the extent to which each of these tracts contributes to the variance in outcome remains unclear. We examined whether diffusion tensor imaging (DTI)‐derived measures of corticospinal and transcallosal tracts predict motor improvement in an experimental neurorehabilitation trial. 15 chronic stroke patients received bihemispheric transcranial direct current stimulation and simultaneous physical/occupational therapy for five consecutive days. Motor impairment was assessed prior to and after the intervention. At baseline, the patients underwent DTI; probabilistic fiber tracking was used to reconstruct the pyramidal tract (PT), alternate descending motor fibers (aMF), and transcallosal fibers connecting primary motor cortices (M1‐M1). Ipsilesional corticospinal tracts (PT, aMF) and M1‐M1 showed significantly decreased fractional anisotropy (FA) and increased directional diffusivities when compared to age‐matched healthy controls. Partial correlations revealed that greater gains in motor function were related to higher FA values and lower directional diffusivities of transcallosal and ipsilesional corticospinal tracts. M1‐M1 diffusivity had the greatest predictive value. An additional slice‐by‐slice analysis of FA values along the corticospinal tracts demonstrated that the more the ipsilesional FA profiles of patients resembled those of healthy controls, the greater their functional improvement. In conclusion, our study shows that DTI‐derived measures can be used to predict functional potential for subsequent motor recovery in chronic stroke patients. Diffusivity parameters of individual tracts and tract combinations may help in assessing a patient's individual recovery potential and in determining optimal neurorehabilitative interventions. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Attention‐related networks in Alzheimer's disease: A resting functional MRI study
Authors: Li Rui , Wu Xia , Fleisher Adam S. , Reiman Eric M. , Chen Kewei , Yao Li
Published: April 2011

In addition to memory deficits, attentional impairment is a common manifestation of Alzheimer's disease (AD). The present study examines the abnormalities of attention‐related functional networks in AD using resting functional MRI (fMRI) technique and evaluates the sensitivity and specificity of these networks as potential biomarkers compared with the default mode network (DMN). Group independent component analysis (Group ICA) was applied to fMRI data from 15 AD patients and 16 normal healthy elderly controls (NC) to derive the dorsal attention network (DAN) and the ventral attention network (VAN) which are respectively responsible for the endogenous attention orienting (“top‐down”) process and the exogenous attention re‐orienting (“bottom‐up”) process. Receiver operating characteristic (ROC) curve analysis was performed for activity in core regions within each of these networks. Functional connectivity analysis revealed disrupted DAN and preserved (less impaired) VAN in AD patients compared with NC, which might indicate impairment of a “top‐down” and intact “bottom‐up” attentional processing mechanisms in AD. ROC curve analysis suggested that activity in the left intraparietal sulcus and left frontal eye field from DAN as well as the posterior cingulate cortex from the DMN could serve as sensitive and specific biomarkers distinguishing AD from NC. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Longitudinal gray matter changes in multiple sclerosis—Differential scanner and overall disease‐related effects
Authors: Bendfeldt Kerstin , Hofstetter Louis , Kuster Pascal , Traud Stefan , Mueller‐Lenke Nicole , Naegelin Yvonne , Kappos Ludwig , Gass Achim , Nichols Thomas E. , Barkhof Frederik , Vrenken Hugo , Roosendaal Stefan D. , Geurts Jeroen J.G. , Radue Ernst‐Wilhelm , Borgwardt Stefan J.
Published: April 2011

Voxel‐based morphometry (VBM) has been used repeatedly in single‐center studies to investigate regional gray matter (GM) atrophy in multiple sclerosis (MS). In multi‐center trials, across‐scanner variations might interfere with the detection of disease‐specific structural abnormalities, thereby potentially limiting the use of VBM. Here we evaluated longitudinally inter‐site differences and inter‐site comparability of regional GM in MS using VBM. Baseline and follow up 3D T1‐weighted magnetic resonance imaging (MRI) data of 248 relapsing‐remitting (RR) MS patients, recruited in two clinical centers, (center1/2: n = 129/119; mean age 42.6 ± 10.7/43.3 ± 9.3; male:female 33:96/44:75; median disease duration 150 [72–222]/116 [60–156]) were acquired on two different 1.5T MR scanners. GM volume changes between baseline and year 2 while controlling for age, gender, disease duration, and global GM volume were analyzed. The main effect of time on regional GM volume was larger in data of center two as compared to center one in most of the brain regions. Differential effects of GM volume reductions occured in a number of GM regions of both hemispheres, in particular in the fronto‐temporal and limbic cortex (cluster P corrected <0.05). Overall disease‐related effects were found bilaterally in the cerebellum, uncus, inferior orbital gyrus, paracentral lobule, precuneus, inferior parietal lobule, and medial frontal gyrus (cluster P corrected <0.05). The differential effects were smaller as compared to the overall effects in these regions. These results suggest that the effects of different scanners on longitudinal GM volume differences were rather small and thus allow pooling of MR data and subsequent combined image analysis. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
How do weak Z–X–X and stronger X–Z–X interactions affect NMR chemical shifts of chalcogenide dihalides, R2Z·X2? Theoretical background on the structural prediction of R2Z·X2 through chemical shifts in solutions
Authors: Tanioku Akito , Nakai Takahito , Hayashi Satoko , Nakanishi Waro
Published: April 2011

The mechanism is clarified for the high applicability of criteria to distinguish molecular complexes (MC) from pseudo‐trigonal bipyramidal adducts (TBP) of chalcogenide dihalogens in solutions, based on the NMR chemical shifts. The criteria are theoretically investigated employing MC and TBP of MeSeMe (1), EtSeEt (3), PhSePh (7), PhSPh (8), and PhSeH (22) with chlorine and/or bromine. The adducts of (CH2CH)2Se (26), H2C(CHCH)2Se (27), and H2C(CHCH)2S (28) are also investigated. Behaviors of total absolute magnetic tensors (σt) for the atoms in question are analyzed separately by the diamagnetic and paramagnetic terms, which well support the observed NMR chemical shifts of the MC and TBP adducts in solutions. As a result, the criteria are thoroughly supported on the basis of theoretical background and the mechanism of criteria is clarified with the diamagnetic and paramagnetic terms. The results shed light on the specific effect of weak ZXX and stronger XZX interactions on the NMR chemical shifts of the adducts, R2Z·X2. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:446–456, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20707
Reciprocal interference between insulin and interferon-alpha signaling in hepatic cells: A vicious circle of clinical significance?
Authors: Franceschini Lisa , Realdon Stefano , Marcolongo Moira , Mirandola Silvia , Bortoletto Gladis , Alberti Alfredo
Published: April 2011

Insulin resistance (IR) is common in chronic hepatitis C (CHC) and associates with reduced virological response to pegylated-interferon (PEG-IFN)/ribavirin therapy, but the underlying mechanisms are still unclear. We have previously shown that, in CHC patients, insulin plasma levels are inversely related to antiviral effect induced by PEG-IFN. Therefore, we investigated the

in vitro

effect of insulin on interferon alpha (IFN-α) intracellular signaling as well as that of IFN-α on insulin signaling. HepG2 cells, preincubated with or without insulin, were stimulated with IFN-α2b and messenger RNA (mRNA) and protein expression of IFN-stimulated genes (ISGs) were measured at different timepoints. The role of intracellular suppressors of cytokine signaling 3 (SOCS3) was evaluated with the small interfering RNA (siRNA) strategy. To assess the effect of IFN-α on insulin signaling, HepG2 were preincubated with or without IFN before addition of insulin and cells were then analyzed for IRS-1 and for Akt/PKB Ser473 phosphorylation. Insulin (100 and 1000 nM) significantly reduced in a dose-dependent fashion IFN-induced gene expression of PKR (

P

= 0.017 and

P

= 0.0017, respectively), MxA (

P

= 0.0103 and

P

= 0.00186), and 2′-5′ oligoadenylatesynthetase 1 (OAS-1) (

P

= 0.002 and

P

= 0.006). Insulin also reduced IFN-α-induced PKR protein expression. Although insulin was confirmed to increase SOCS3 expression, siRNA SOCS3 did not restore ISG expression after insulin treatment. IFN-α was found to reduce, in a dose-dependent fashion, IRS-1 gene expression as well as Akt/PKB Ser473 phosphorylation induced by insulin.

Conclusion:

These results provide evidence of reciprocal interference between insulin and IFN-α signaling in liver cells. These findings may contribute to understand the role of insulin in CHC: IR might be favored by endogenous cytokines including IFN-α, and the resulting hyperinsulinemia then reduces the antiviral response to exogenous IFN in a vicious circle of clinical significance. (Hepatology 2011;)
Novel engineered targeted interferon-gamma blocks hepatic fibrogenesis in mice
Authors: Bansal Ruchi , Prakash Jai , Post Eduard , Beljaars Leonie , Schuppan Detlef , Poelstra Klaas
Published: April 2011

Liver fibrogenesis is a process tightly controlled by endogenous anti- and pro-fibrogenic factors. Interferon gamma (IFNγ) is a potent antifibrogenic cytokine

in vitro

and might therefore represent a powerful therapeutic entity. However, its poor pharmacokinetics and adverse effects, due to the presence of IFNγ receptors on nearly all cells, prevented its clinical application so far. We hypothesized that delivery of IFNγ specifically to the disease-inducing cells and concurrently avoiding its binding to nontarget cells might increase therapeutic efficacy and avoid side effects. We conjugated IFNγ to a cyclic peptide recognizing the platelet-derived growth factor beta receptor (PDGFβR) which is strongly up-regulated on activated hepatic stellate cells (HSC), the key effector cells responsible for hepatic fibrogenesis. The IFNγ conjugates were analyzed

in vitro

for PDGFβR-specific binding and biological effects and

in vivo

in acute (early) and chronic (progressive and established) carbon-tetrachloride-induced liver fibrosis in mice. The targeted-IFNγ construct showed PDGFβR-specific binding to fibroblasts and HSC and inhibited their activation

in vitro
.
In vivo
, the targeted-IFNγ construct attenuated local HSC activation in an acute liver injury model. In the established liver fibrosis model, it not only strongly inhibited fibrogenesis but also induced fibrolysis. In contrast, nontargeted IFNγ was ineffective in both models. Moreover, in contrast to unmodified IFNγ, our engineered targeted-IFNγ did not induce IFNγ-related side effects such as systemic inflammation, hyperthermia, elevated plasma triglyceride levels, and neurotropic effects.

Conclusion:

This study presents a novel HSC-targeted engineered-IFNγ, which in contrast to systemic IFNγ, blocked liver fibrogenesis and is devoid of side effects, by specifically acting on the key pathogenic cells within the liver. (Hepatology 2011;)
Comparative study of hydrophilic and hydrophobic ionic liquids for observing cultured human cells by scanning electron microscopy
Authors: Ishigaki Yasuhito , Nakamura Yuka , Takehara Teruaki , Kurihara Takayuki , Koga Hironori , Takegami Tsutomu , Nakagawa Hideaki , Nemoto Noriko , Tomosugi Naohisa , Kuwabata Susumu , Miyazawa Shichiro
Published: April 2011

An ionic liquid (IL) is a salt that remains in the liquid state at room temperature. It does not vaporize under vacuum and imparts electrical conductivity to samples for observation by scanning electron microscopy (SEM). Recently, the usefulness of ILs has been widely recognized. In our previous study, one of the ILs 1‐ethyl‐3‐methylimidazolium tetrafluoroborate (EtMelm+BF4−) was used for SEM analysis of biological samples. In comparison with the conventional method, samples prepared using EtMelm+BF4− provided more detailed SEM images of the cell ultrastructure, enabling the observation of protrusions. In addition, the IL treatment is a less time consuming and simple method that does not include dehydration, drying, and conductivity treatments, which are an essential parts of the conventional method. In this study, we compared the usefulness of four hydrophobic and three hydrophilic ILs for SEM to observe fixed cultured human A549 cells. All ILs worked well to prevent “charge‐up” effect for SEM observation. However, the hydrophilic ILs tended to provide clearer images than the hydrophobic ILs. We concluded that various ILs can be used for SEM sample preparation and their application to a wide range of fields is anticipated in future. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.
Shape Memory Polyurethanes from Renewable Polyols Obtained by ATMET Polymerization of Glyceryl Triundec‐10‐enoate and 10‐Undecenol
Authors: del Río Enrique , Lligadas Gerard , Ronda Juan Carlos , Galià Marina , Cádiz Virginia , Meier Michael A. R.
Published: April 2011

The synthesis of branched polyols from glyceryl triundec‐10‐enoate by acyclic triene metathesis polymerization (ATMET) is reported. 10‐Undecenol is used as a monofunctional comonomer to end‐cap polymer chains, functionalize the periphery of the resulting branched materials, and to control the molecular weight. The thus obtained castor oil derived polyols are reacted with 4,4′‐methylenebis(phenylisocyanate) (MDI) to yield a series of semicrystalline polyurethane networks. The investigation of the thermal stability and the thermomechanical and mechanical properties of these thermosets revealed good shape memory properties.

magnified image
A randomized, double‐blind trial of transcranial electrostimulation in early Parkinson's disease
Authors: Shill Holly A. , Obradov Sanja , Katsnelson Yakov , Pizinger Ray
Published: April 2011

We studied the effects of noninvasive transcranial electrical stimulation on the motor and psychological symptoms of early Parkinson's disease. Twenty‐three subjects were treated with 10 days of placebo versus active treatment and then followed for 14 weeks. Baseline off medication Unified Parkinson's Disease Rating Scale parts I–III was 29.4 ± 10.0. The primary end point, Unified Parkinson's Disease Rating Scale in week 2 following treatment, reduced by 5.3 ± 9.7 for those in active treatment and 7.7 ± 4.8 for those receiving placebo (not significant). Similarly, no significant differences were seen in the Hamilton Anxiety Scale, Geriatric Depression Scale, and Epworth Sleepiness Scale over the duration of the study. The treatment was well tolerated without device‐related adverse events. Despite the negative study, nonpharmacological approaches should continue to be pursued in Parkinson's disease, as they are generally well received by patients. © 2011 Movement Disorder Society
Genetic LRRK2 models of Parkinson's disease: Dissecting the pathogenic pathway and exploring clinical applications
Authors: Yue Zhenyu , Lachenmayer M. Lenard
Published: April 2011

Dominantly inherited mutations in leucine‐rich repeat kinase 2 are the most common cause of familial Parkinson's disease. Understanding leucine‐rich repeat kinase 2 biology and pathophysiology is central to the elucidation of Parkinson's disease etiology and development of disease intervention. Recently, a number of genetic mouse models of leucine‐rich repeat kinase 2 have been reported utilizing different genetic approaches. Some similarities in Parkinson's disease‐related pathology emerge in these genetic models despite lack of substantial neuropathology and clinical syndromes of Parkinson's disease. The systematic characterization of these models has begun to shed light on leucine‐rich repeat kinase 2 biology and pathophysiology and is expected to offer the identification and validation of drug targets. In this review, we summarize the progress of genetic leucine‐rich repeat kinase 2 mouse models and discuss their utility in understanding much needed knowledge regarding early‐stage (presymptomatic) disease progression, identifying drug targets, and exploring the potential to aid compound screening focused on inhibitors of kinase activity of leucine‐rich repeat kinase 2. © 2011 Movement Disorder Society
The modified bradykinesia rating scale for Parkinson's disease: Reliability and comparison with kinematic measures
Authors: Heldman Dustin A. , Giuffrida Joseph P. , Chen Robert , Payne Megan , Mazzella Filomena , Duker Andrew P. , Sahay Alok , Kim Sang Jin , Revilla Fredy J. , Espay Alberto J.
Published: April 2011

Bradykinesia encompasses slowness, decreased movement amplitude, and dysrhythmia. Unified Parkinson's Disease Rating Scale–based bradykinesia‐related items require that clinicians condense abnormalities in speed, amplitude, fatiguing, hesitations, and arrests into a single score. The objective of this study was to evaluate the reliability of a modified bradykinesia rating scale, which separately assesses speed, amplitude, and rhythm and its correlation with kinematic measures from motion sensors. Fifty patients with Parkinson's disease performed Unified Parkinson's Disease Rating Scale–directed finger tapping, hand grasping, and pronation–supination while wearing motion sensors. Videos were rated blindly and independently by 4 clinicians. The modified bradykinesia rating scale and Unified Parkinson's Disease Rating Scale demonstrated similar inter‐ and intrarater reliability. Raters placed greater weight on amplitude than on speed or rhythm when assigning a Unified Parkinson's Disease Rating Scale score. Modified bradykinesia rating scale scores for speed, amplitude, and rhythm correlated highly with quantitative kinematic variables. The modified bradykinesia rating scale separately captures bradykinesia components with interrater and intrarater reliability similar to that of the Unified Parkinson's Disease Rating Scale. Kinematic sensors can accurately quantify speed, amplitude, and rhythm to aid in the development and evaluation of novel therapies in Parkinson's disease. © 2011 Movement Disorder Society
Mechanistic issues concerning cancer prevention by tea catechins
Authors: Yang Chung S. , Wang Hong
Published: April 2011

The cancer preventive activities of tea (Camellia sinensis, Theaceae) have been demonstrated in animal models for cancers at different organ sites and suggested by some epidemiological studies. Many mechanisms for cancer prevention have been proposed based on studies in cell lines, which demonstrated the modulation of signal transduction and metabolic pathways by (−)‐epigallocatechin‐3‐gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events may result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, it is not known whether these are the molecular mechanisms of inhibition of carcinogenesis in animals and humans. This article discusses the key issues involved in extrapolating results from cell line studies to mechanistic information in vivo and in translating animal studies to human cancer prevention.
Electrophysiological entrapment syndromes in chronic inflammatory demyelinating polyneuropathy
Authors: Rajabally Yusuf A. , Narasimhan Manisha
Published: April 2011

We do not know if peripheral nerves are more susceptible to entrapment syndromes in chronic inflammatory demyelinating polyneuropathy (CIDP). We studied 31 prospectively recruited patients with CIDP. We determined whether entrapment zones were more frequently affected by demyelination than adjacent segments. The median, ulnar, and fibular nerves were studied at the wrist, elbow, and fibular head bilaterally. Motor conduction velocity and motor conduction block were evaluated at entrapment sites and compared with contiguous segments. Demyelination was significantly more frequent for ulnar and fibular nerves away from entrapment sites. No significant difference was observed for median nerves. CIDP is not associated with increased frequency of demyelination at entrapment sites. The presence of diffuse entrapment neuropathies at compression sites does not favor a diagnosis of CIDP. Although electrophysiological study of entrapment sites is not diagnostically useful in CIDP, it may help distinguish it from other neuropathies and confirm clinically relevant, surgically treatable compressions. Muscle Nerve 44: 444–447, 2011
Quantification of in vivo metabolic kinetics of hyperpolarized pyruvate in rat kidneys using dynamic 13C MRSI
Authors: Xu Tao , Mayer Dirk , Gu Meng , Yen Yi‐Fen , Josan Sonal , Tropp James , Pfefferbaum Adolf , Hurd Ralph , Spielman Daniel
Published: April 2011

With signal‐to‐noise ratio enhancements on the order of 10,000‐fold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products in vivo. Although hyperpolarized [1‐13C]pyruvate, in particular, has been used to demonstrate metabolic activities in various animal models, robust quantification and metabolic modeling remain important areas of investigation. Enzyme saturation effects are routinely seen with commonly used doses of hyperpolarized [1‐13C]pyruvate; however, most metrics proposed to date, including metabolite ratios, time‐to‐peak of metabolic products and single exchange rate constants, fail to capture these saturation effects. In addition, the widely used small‐flip‐angle excitation approach does not correctly model the inflow of fresh downstream metabolites generated proximal to the target slice, which is often a significant factor in vivo. In this work, we developed an efficient quantification framework employing a spiral‐based dynamic spectroscopic imaging approach. The approach overcomes the aforementioned limitations and demonstrates that the in vivo 13C labeling of lactate and alanine after a bolus injection of [1‐13C]pyruvate is well approximated by saturatable kinetics, which can be mathematically modeled using a Michaelis–Menten‐like formulation, with the resulting estimated apparent maximal reaction velocity Vmax and apparent Michaelis constant KM being unbiased with respect to critical experimental parameters, including the substrate dose, bolus shape and duration. Although the proposed saturatable model has a similar mathematical formulation to the original Michaelis–Menten kinetics, it is conceptually different. In this study, we focus on the 13C labeling of lactate and alanine and do not differentiate the labeling mechanism (net flux or isotopic exchange) or the respective contribution of various factors (organ perfusion rate, substrate transport kinetics, enzyme activities and the size of the unlabeled lactate and alanine pools) to the labeling process. Copyright © 2011 John Wiley & Sons, Ltd.
Bilateral hilar lymphadenopathy due to Chlamydia pneumoniae infection
Authors: Fretzayas Andrew , Moustaki Maria , Priftis Konstantinos N. , Yiallouros Panagiotis , Paschalidou Maria , Nicolaidou Polyxeni
Published: April 2011

We here report a 5‐year‐old boy who presented with cough and bilateral hilar lymphadenopathy with a family history of sarcoidosis. The laboratory investigations did not confirm this diagnosis. The child was serologically proven to have Chlamydia pneumoniae infection. He responded well to a course of erythromycin resulting in complete resolution of his symptoms and the presenting radiographic findings on his initial chest X‐ray. Pediatr. Pulmonol. 2011; 46:1038–1040. © 2011 Wiley‐Liss, Inc.
Clinical outcomes in infants with cystic fibrosis transmembrane conductance regulator (CFTR) related metabolic syndrome
Authors: Ren Clement L. , Desai Harsh , Platt Mary , Dixon Marissa
Published: April 2011

An unavoidable outcome of cystic fibrosis newborn screening (CF NBS) programs is the detection of infants with an indeterminate diagnosis. The United States CF Foundation recently proposed the term cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS) to describe infants with elevated immunoreactive trypsinogen (IRT) on NBS who do not meet diagnostic criteria for CF. The objective of this study was to describe the clinical outcomes of infants with CRMS identified through an IRT/DNA algorithm. We reviewed the records of all infants with CRMS diagnosed at our CF Center from 2002 to 2010. We identified 12 infants, and compared them to 27 infants diagnosed with CF by NBS. Compared to CF patients, CRMS patients were more likely to be pancreatic sufficient as assessed by fecal elastase measurement (100% vs. 8%, P < 0.01). Their weight for age percentile was normal from birth. A positive oropharyngeal (OP) culture for Pseudomonas aeruginosa (Pa) was found in 25% of CRMS patients. One patient with the F508del/R117H/7T genotype was reassigned the diagnosis of CF after he had a positive OP culture for Pa, and his follow up sweat Cl at 1 year of life was 73 mmol/L. CF patients were more likely to receive oral antibiotics and be hospitalized for pulmonary symptoms. Our results indicate that CRMS patients can develop signs of CF disease, but have a milder clinical course than CF infants. Close initial monitoring of these patients is warranted. Pediatr. Pulmonol. 2011; 46:1079–1084. © 2011 Wiley Periodicals, Inc.
Visual servoing for a US‐guided therapeutic HIFU system by coagulated lesion tracking: a phantom study
Authors: Seo Joonho , Koizumi Norihiro , Funamoto Takakazu , Sugita Naohiko , Yoshinaka Kiyoshi , Nomiya Akira , Homma Yukio , Matsumoto Yoichiro , Mitsuishi Mamoru
Published: April 2011

Background

Applying ultrasound (US)‐guided high‐intensity focused ultrasound (HIFU) therapy for kidney tumours is currently very difficult, due to the unclearly observed tumour area and renal motion induced by human respiration. In this research, we propose new methods by which to track the indistinct tumour area and to compensate the respiratory tumour motion for US‐guided HIFU treatment.

Methods

For tracking indistinct tumour areas, we detect the US speckle change created by HIFU irradiation. In other words, HIFU thermal ablation can coagulate tissue in the tumour area and an intraoperatively created coagulated lesion (CL) is used as a spatial landmark for US visual tracking. Specifically, the condensation algorithm was applied to robust and real‐time CL speckle pattern tracking in the sequence of US images. Moreover, biplanar US imaging was used to locate the three‐dimensional position of the CL, and a three‐actuator system drives the end‐effector to compensate for the motion. Finally, we tested the proposed method by using a newly devised phantom model that enables both visual tracking and a thermal response by HIFU irradiation.

Results

In the experiment, after generation of the CL in the phantom kidney, the end‐effector successfully synchronized with the phantom motion, which was modelled by the captured motion data for the human kidney. The accuracy of the motion compensation was evaluated by the error between the end‐effector and the respiratory motion, the RMS error of which was approximately 2 mm.

Conclusion

This research shows that a HIFU‐induced CL provides a very good landmark for target motion tracking. By using the CL tracking method, target motion compensation can be realized in the US‐guided robotic HIFU system. Copyright © 2011 John Wiley & Sons, Ltd.
Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [11C] P943: A positron emission tomography study in Papio anubis
Authors: Ridler Khanum , Plisson Christophe , Rabiner Eugenii A. , Gunn Roger N. , Easwaramoorthy Balu , Abi‐Dargham Anissa , Laruelle Marc , Slifstein Mark
Published: April 2011

[11C] P943 is a recently developed PET radiotracer for serotonin 5‐HT1B receptors. We characterized a number of its in vivo pharmacokinetic properties, including the evaluation of its two stereo‐isomers, saturability of specific binding, selectivity for 5‐HT1B and 5‐HT1D receptors, and vulnerability to pharmacologically induced increases in endogenous 5‐HT levels. Six isoflurane‐anesthetized baboons were scanned with [11C] P943 at baseline, and following various pharmacological manipulations. The interventions included the administration of pharmacological doses of P943, SB‐616234‐S (a 5‐HT1B selective antagonist), SB‐714786 (a 5‐HT1D selective antagonist), as well as the administration of 5‐HT releasing agents (fenfluramine, amphetamine) and 5‐HT reuptake inhibitor (citalopram). [11C] P943 was observed to bind saturably and specifically to 5‐HT1B receptors and to be sensitive to all three challenges known to alter 5‐HT levels in the proximity of receptors. [11C] P943 shows promise as a tracer to image serotonin function in healthy subjects as well as subjects with psychiatric or neurologic conditions. Synapse, 2011. © 2011 Wiley‐Liss, Inc.
Minimally Invasive Technique for Release of Dupuytren's Contracture: Segmental Fasciectomy through Multiple Transverse Incisions
Authors: Shin Eon Kyu , Jones Neil Ford
Published: April 2011

Background

A multitude of operative approaches have been described for treatment of Dupuytren's contracture. A less-invasive technique of segmental fasciectomies performed through multiple small transverse incisions is presented.

Methods

Seventy-three digits in 37 patients were treated with segmental fasciectomies. The results of 34 digits in 14 patients are described with subsequent follow-up longer than 2 years.

Results

Metacarpophalangeal joint extension improved from a mean of 32.5° to 2.2°, while proximal interphalangeal joint extension improved from 22.9° to 4.1°. Patients subjectively rated their surgical outcomes as excellent or good in 91.2% of cases. No recurrence of the disease was noted, though extension of the disease to adjacent digits was observed in three patients.

Conclusions

Though this approach is technically demanding and requires the help of a skilled assistant, this preliminary study supports our contention that this less-extensive procedure allows excellent correction of contractures; results in mild postoperative pain; and permits a rapid return of finger flexion with satisfactory long-term results so far at 2-years follow-up.
Corrigendum to: Phylogenetics of hopbushes and pepperflowers (Dodonaea, Diplopeltis - Sapindaceae), based on nuclear ribosomal ITS and partial ETS sequences incorporating secondary-structure models
Authors: Harrington Mark G. , Gadek Paul A.
Published: April 2011

Hopbushes and pepperflowers (Dodonaea, Diplopeltis ? Sapindaceae) are important components of Australia's arid zone and sclerophyll and temperate forests and woodlands. Phylogenetic analyses of nuclear ribosomal ITS and partial ETS sequences for near-complete sampling of both genera were performed using a Bayesian statistical method and RNA specific models of nucleotide evolution that incorporate secondary structure (separate models for stems and loops). Diplopeltis is paraphyletic. Diplopeltis stuartii is not closer to other species of the genus than it is to species outside the genus. There are also several evolutionary elements in the molecular data that support D. stuartii as distinct from the other members of the genus. The monophyly of Dodonaea as redefined here to include all species of Distichostemon is unequivocally supported by the molecular data and the morphological synapomorphies of petal-less flowers with a highly reduced intrastaminal disk that is absent in staminate flowers. There do not appear to be any obvious evolutionary trends in the morphological characters (leaf and capsule form, presence or absence of aril, or breeding system) that have been previously used to group taxa. However, there are some morphological characters that may be useful to delineate some of the clades recovered in the present molecular study. New combinations in Dodonaea are made for all species of Distichostemon.
Australian species of Elaphomyces (Elaphomycetaceae, Eurotiales, Ascomycota)
Authors: Castellano Michael A. , Trappe James M. , Vernes Karl
Published: April 2011

The sequestrate ascomycete genus Elaphomyces is described and illustrated from Australia. The following thirteen new species are described: Elaphomyces aurantias, E. austrogranulatus, E. chlorocarpus, E. cooloolanus, E. coralloideus, E. laetiluteus, E. nothofagi, E. pedicellaris, E. queenslandicus, E. rugosisporus, E. suejoyceae, E. symeae, and E. timgroveii. A key is provided to all Elaphomyces species from Australia.
Cysteine shotgun–mass spectrometry (CS-MS) reveals dynamic sequence of protein structure changes within mutant and stressed cells
Authors: Krieger Christine C. , An Xiuli , Tang Hsin-Yao , Mohandas Narla , Speicher David W. , Discher Dennis E.
Published: April 2011

Questions of if and when protein structures change within cells pervade biology and include questions of how the cytoskeleton sustains stresses on cells—particularly in mutant versus normal cells. Cysteine shotgun labeling with fluorophores is analyzed here with mass spectrometry of the spectrin–actin membrane skeleton in sheared red blood cell ghosts from normal and diseased mice. Sheared samples are compared to static samples at 37 °C in terms of cell membrane intensity in fluorescence microscopy, separated protein fluorescence, and tryptic peptide modification in liquid chromatography–tandem mass spectrometry (LC-MS/MS). Spectrin labeling proves to be the most sensitive to shear, whereas binding partners ankyrin and actin exhibit shear thresholds in labeling and both the ankyrin-binding membrane protein band 3 and the spectrin–actin stabilizer 4.1R show minimal differential labeling. Cells from 4.1R-null mice differ significantly from normal in the shear-dependent labeling of spectrin, ankyrin, and band 3: Decreased labeling of spectrin reveals less stress on the mutant network as spectrin dissociates from actin. Mapping the stress-dependent labeling kinetics of α- and β-spectrin by LC-MS/MS identifies Cys in these antiparallel chains that are either force-enhanced or force-independent in labeling, with structural analyses indicating the force-enhanced sites are sequestered either in spectrin’s triple-helical domains or in interactions with actin or ankyrin. Shear-sensitive sites identified comprehensively here in both spectrin and ankyrin appear consistent with stress relief through forced unfolding
followed by
cytoskeletal disruption.
Caenorhabditis elegans
chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells
Authors: Xiao Yu , Bedet Cécile , Robert Valérie J. P. , Simonet Thomas , Dunkelbarger Steve , Rakotomalala Cédric , Soete Gwen , Korswagen Hendrik C. , Strome Susan , Palladino Francesca
Published: April 2011

Methylation of histone H3 lysine 4 (H3K4me), a mark associated with gene activation, is mediated by SET1 and the related mixed lineage leukemia (MLL) histone methyltransferases (HMTs) across species. Mammals contain seven H3K4 HMTs, Set1A, Set1B, and MLL1–MLL5. The activity of SET1 and MLL proteins relies on protein–protein interactions within large multisubunit complexes that include three core components: RbBP5, Ash2L, and WDR5. It remains unclear how the composition and specificity of these complexes varies between cell types and during development.
Caenorhabditis elegans
contains one SET1 protein, SET-2, one MLL-like protein, SET-16, and single homologs of RbBP5, Ash2L, and WDR5. Here we show that SET-2 is responsible for the majority of bulk H3K4 methylation at all developmental stages. However, SET-2 and absent, small, or homeotic discs 2 (ASH-2) are differentially required for tri- and dimethylation of H3K4 (H3K4me3 and -me2) in embryos and adult germ cells. In embryos, whereas efficient H3K4me3 requires both SET-2 and ASH-2, H3K4me2 relies mostly on ASH-2. In adult germ cells by contrast, SET-2 serves a major role whereas ASH-2 is dispensable for H3K4me3 and most H3K4me2. Loss of SET-2 results in progressive sterility over several generations, suggesting an important function in the maintenance of a functional germ line. This study demonstrates that individual subunits of SET1-related complexes can show tissue specificity and developmental regulation and establishes
C. elegans
as a model to study SET1-related complexes in a multicellular organism.
Antimicrobials
Authors: Török M. Estée , Cooke Fiona J. , Moran Ed
Published: April 2011

Abstracts and keywords to be supplied.
Ethical issues
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

Chapter 1 discusses four clinical scenarios andapplyies the principles of ethics in order to reach a balanced compromise that can help provide a path through uncertainty. The chapter also looks at consent and compliance, and euthanasia.
Non-medical prescribing
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter gives a very short overview to non-medical prescribing.
Art therapy
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter provides a very brief introduction to art therapy.
The terminal phase
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter discusses the terminal phase, including common problems in the last 48 hours, the Liverpool Care Pathway for the dying patient, and international perspectives in care pathways.
Legal and professional standards of care
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter on legal and professional standards of care covers the Mental Capacity Act 2005 (MCA), and clinical negligence.
Genograms
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter consists of a diagram showing genograms.
Peripheral nerve assessment
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter consists of a diagram showing peripheral nerve assessment.
Travelling abroad
Authors: Watson Max , Lucas Caroline , Hoy Andrew , Wells Jo
Published: April 2011

This chapter briefly covers issues surrounding travelling abroad when terminally ill.
Intracellular pH distribution as a cell health indicator in
Saccharomyces cerevisiae
Authors: Aabo Thomas , Glückstad Jesper , Siegumfeldt Henrik , Arneborg Nils
Published: April 2011

Internal pH regulation is vital for many cell functions, including transport mechanisms and metabolic enzyme activity. More specifically, transport mechanisms are to a wide degree governed by internal pH distributions. We introduce the term standard deviation of the intracellular pH (s.d.(pH
int
)) to describe the internal pH distributions. The cellular pH distributional response to external stress such as heat has not previously been determined. In this study, the intracellular pH (pH
i
) and the s.d.(pH
int
) of
Saccharomyces cerevisiae
cells exposed to supralethal temperatures were measured using fluorescence ratio imaging microscopy (FRIM). An exponential decline in pH
i
was observed after an initial small decline. For the first time, we report the use of FRIM for determining
in vivo
plasma membrane proton permeability coefficients in yeast. Furthermore, the exponential decay of pH
i
and the rupture of the cell plasma membrane, as measured by propidium iodide staining, at 70°C were not simultaneous but were separated by a significant temporal difference. Finally, a nonlinear relationship between the pH
i
and s.d.(pH
int
) was found; i.e. the s.d.(pH
int
) was significantly more sensitive to supralethal temperatures than pH
i
. s.d.(pH
int
) is therefore proposed as an early health/vitality indicator in
S. cerevisiae
cells exposed to heat stress.
Role of fimV in type II secretion system-dependent protein secretion of Pseudomonas aeruginosa on solid medium
Authors: Michel Gérard P. F. , Aguzzi Anthony , Ball Geneviève , Soscia Chantal , Bleves Sophie , Voulhoux Romé
Published: April 2011

Although classical type II secretion systems (T2SSs) are widely present in Gram-negative bacteria, atypical T2SSs can be found in some species. In Pseudomonas aeruginosa, in addition to the classical T2SS Xcp, it was reported that two genes, xphA and xqhA, located outside the xcp locus were organized in an operon (PaQa) which encodes the orphan PaQa subunit. This subunit is able to associate with other components of the classical Xcp machinery to form a functional hybrid T2SS. In the present study, using a transcriptional lacZ fusion, we found that the PaQa operon was more efficiently expressed (i) on solid LB agar than in liquid LB medium, (ii) at 25 °C than at 37 °C and (iii) at an early stage of growth. These results suggested an adaptation of the hybrid system to particular environmental conditions. Transposon mutagenesis led to the finding that vfr and fimV genes are required for optimal expression of the orphan PaQa operon in the defined growth conditions used. Using an original culturing device designed to monitor secretion on solid medium, the ring-plate system, we found that T2SS-dependent secretion of exoproteins, namely the elastase LasB, was affected in a fimV deletion mutant. Our findings led to the discovery of an interplay between FimV and the global regulator Vfr triggering the modulation of the level of Vfr and consequently the modulation of T2SS-dependent secretion on solid medium.
Interaction of Bacteroides fragilis and Bacteroides thetaiotaomicron with the kallikrein–kinin system
Authors: Murphy Elizabeth C. , Mörgelin Matthias , Cooney Jakki C. , Frick Inga-Maria
Published: April 2011

Many bacterial pathogens interfere with the contact system (kallikrein–kinin system) in human plasma. Activation of this system has two consequences: cleavage of high-molecular-mass kininogen (HK) resulting in release of the potent proinflammatory peptide bradykinin, and initiation of the intrinsic pathway of coagulation. In this study, two species of the Gram-negative anaerobic commensal organismBacteroides, namelyBacteroides fragilisandBacteroides thetaiotaomicron, were found to bind HK and fibrinogen, the major clotting protein, from human plasma as shown by immunoelectron microscopy and Western blot analysis. In addition, theseBacteroidesspecies were capable of activating the contact system at its surface leading to a significant prolongation of the intrinsic coagulation time and also to the release of bradykinin. Members of the genusBacteroideshave been known to act as opportunistic pathogens outside the gut, withB. fragilisbeing the most common isolate from clinical infections, such as intra-abdominal abscesses and bacteraemia. The present results thus provide more insight into howBacteroidesspecies cause infection.
Regulatory Hotspots Are Associated with Plant Gene Expression under Varying Soil Phosphorus Supply in Brassica rapa
Authors: Hammond John P. , Mayes Sean , Bowen Helen C. , Graham Neil S. , Hayden Rory M. , Love Christopher G. , Spracklen William P. , Wang Jun , Welham Sue J. , White Philip J. , King Graham J. , Broadley Martin R.
Published: April 2011

Gene expression is a quantitative trait that can be mapped genetically in structured populations to identify expression quantitative trait loci (eQTL). Genes and regulatory networks underlying complex traits can subsequently be inferred. Using a recently released genome sequence, we have defined cis- and trans-eQTL and their environmental response to low phosphorus (P) availability within a complex plant genome and found hotspots of trans-eQTL within the genome. Interval mapping, using P supply as a covariate, revealed 18,876 eQTL. trans-eQTL hotspots occurred on chromosomes A06 and A01 within Brassica rapa; these were enriched with P metabolism-related Gene Ontology terms (A06) as well as chloroplast- and photosynthesis-related terms (A01). We have also attributed heritability components to measures of gene expression across environments, allowing the identification of novel gene expression markers and gene expression changes associated with low P availability. Informative gene expression markers were used to map eQTL and P use efficiency-related QTL. Genes responsive to P supply had large environmental and heritable variance components. Regulatory loci and genes associated with P use efficiency identified through eQTL analysis are potential targets for further characterization and may have potential for crop improvement.
MLN4924 Is an Efficient Inhibitor of NEDD8 Conjugation in Plants
Authors: Hakenjos Jana Pia , Richter René , Dohmann Esther Mirjam Natascha , Katsiarimpa Anthi , Isono Erika , Schwechheimer Claus
Published: April 2011

The conjugation of the ubiquitin-like modifier NEURAL PRECURSOR CELL-EXPRESSED DEVELOPMENTALLY DOWN-REGULATED PROTEIN8/RELATED TO UBIQUITIN1 (NEDD8/RUB1; neddylation) is best known as an important posttranslational modification of the cullin subunits of cullin-RING-type E3 ubiquitin ligases (CRLs). MLN4924 has recently been described as an inhibitor of NEDD8-ACTIVATING ENZYME1 (NAE1) in human. Here, we show that MLN4924 is also an effective and specific inhibitor of NAE1 enzymes from Arabidopsis (Arabidopsis thaliana) and other plant species. We found that MLN4924-treated wild-type seedlings have phenotypes that are highly similar to phenotypes of mutants with a partial defect in neddylation and that such neddylation-defective mutants are hypersensitive to MLN4924 treatment. We further found that MLN4924 efficiently blocks the neddylation of cullins in Arabidopsis and that MLN4924 thereby interferes with the degradation of CRL substrates and their downstream responses. MLN4924 treatments also induce characteristic phenotypes in tomato (Solanum lycopersicum), Cardamine hirsuta, and Brachypodium distachyon. Interestingly, MLN4924 also blocks the neddylation of a number of other NEDD8-modified proteins. In summary, we show that MLN4924 is a versatile and specific neddylation inhibitor that will be a useful tool to examine the role of NEDD8- and CRL-dependent processes in a wide range of plant species.