bluuebunny/crossref_metadata_2025 huggingface dataset:
Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8
Authors: Blevins James E. , Morton Gregory J. , Williams Diana L. , Caldwell David W. , Bastian Lloyd S. , Wisse Brent E. , Schwartz Michael W. , Baskin Denis G.
Published: December 2008

Melanocortin 4 receptors (MC4R) are hypothesized to mediate the central nervous system actions of leptin to enhance the satiety effects of cholecystokinin (CCK). To further elucidate this mechanism, we confirmed that peripheral administration of CCK-8 is less effective in producing this effect in MC4R-deficient mice (MC4R−/−). Whereas intraperitoneal (ip) CCK-8 at 0.75 nmol/kg lean body mass (lbm) suppressed food intake in wild-type mice, CCK-8 doses of 7.5 nmol/kg lbm were required to attenuate food intake in MC4R−/− mice. To determine whether melanocortin signaling in the hypothalamic paraventricular nucleus (PVN) participates in regulating this CCK satiety response, we administered the MC3/MC4R antagonist, SHU9119, into the PVN of rats before ip CCK-8 administration. PVN administration of SHU9119 attenuated the ability of CCK-8 to reduce 30-min food intake by 20%. To determine whether MC4R are expressed by PVN neurons that project directly to hindbrain nuclei involved in the satiety response to ip CCK-8, the retrograde tracer fluorescent cholera toxin subunit B was injected into the nucleus tractus solitarius (NTS) of the hindbrain. After 4 days, labeled PVN neurons were collected by laser capture microdissection and found to express MC4R mRNA by quantitative RT-PCR analysis. These data provide evidence for a neuroanatomical link between hypothalamic melanocortin signaling in the PVN and NTS neurons that regulate food intake. These findings highlight the contribution of melanocortin signaling in the PVN toward regulating the satiety effects of CCK-8 while acknowledging that melanocortin-dependent pathways in other brain regions and/or melanocortin-independent mechanisms are also important in this mechanism.
Is baroreflex control of sympathetic activity and heart rate active in the preterm fetal sheep?
Authors: Booth Lindsea C. , Malpas Simon C. , Barrett Carolyn J. , Guild Sarah-Jane , Gunn Alistair J. , Bennet Laura
Published: December 2008

The arterial baroreflex is a fundamental reflex that buffers rapid changes in arterial blood pressure (BP) via regulation of the heart rate and sympathetic nerve activity to the vasculature. In adults a sigmoidal relationship between BP and both heart rate and sympathetic nerve activity is well documented. Its role in blood pressure control before birth is unclear. Preterm babies have a high incidence of low BP, especially in the first few days of life, which could be related, in part, to immaturity of the baroreflex. In the present study, we investigated the baroreflex control of fetal heart rate and renal sympathetic nerve activity (RSNA) in preterm fetal sheep in utero (102 ± 1 days of gestation; term 140 days). Phenylephrine was associated with a significant increase in BP from 38 ± 2 to 58 ± 3 mmHg and a decrease in heart rate (HR) from 177 ± 4 to 116 ± 8 beats per minute (bpm). Sodium nitroprusside was associated with a significant fall in BP from 38 ± 2 to 26 ± 1 mmHg and an increase in HR from 182 ± 4 to 274 ± 8 bpm. However, the time between the 50% changes in BP and HR was significantly greater after hypotension than hypertension (31 ± 8 s vs. 14 ± 5 s, P < 0.05). No significant changes in RSNA occurred with either stimulus. This suggests that there are different maturational tempos for the components of the central autonomic response to altered blood pressure.
Anterograde transneuronal viral tract tracing reveals central sensory circuits from white adipose tissue
Authors: Song C. Kay , Schwartz Gary J. , Bartness Timothy J.
Published: December 2008

The origins of the sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) have been defined using the transneuronal viral retrograde tract tracer, pseudorabies virus. Activation of this SNS innervation is acknowledged as the principal initiator of WAT lipolysis. The central control of WAT lipolysis may require neural feedback to a brain-SNS-WAT circuit via WAT afferents. Indeed, conventional tract tracing studies have demonstrated that peripheral pseudounipolar dorsal root ganglion (DRG) sensory cells innervate WAT. The central nervous system projections of WAT afferents remain uncharted, however, and form the focus of the present study. We used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer, to define the afferent circuits projecting from WAT to the central nervous system. Siberian hamster inguinal (IWAT) or epididymal WAT was injected with H129 and the neuraxis processed for HSV-1 immunoreactivity. We found substantial overlap in the pattern of WAT sensory afferent projections with multiple SNS outflow sites along the neuraxis, suggesting the possibility of WAT sensory-SNS circuits that could regulate WAT SNS drive and thereby lipolysis. Previously, we demonstrated that systemic 2-deoxy-d-glucose (2DG) elicited increases in the SNS drive to IWAT. Here, we show that systemic 2DG administration also significantly increases multiunit spike activity arising from decentralized IWAT afferents. Collectively, these data provide structural and functional support for the existence of a sensory WAT pathway to the brain, important in the negative feedback control of lipid mobilization.
High-salt diet enhances mouse aortic relaxation through adenosine A2Areceptor via CYP epoxygenases
Authors: Nayeem Mohammed A. , Ponnoth Dovenia S. , Boegehold Matthew A. , Zeldin Darryl C. , Falck John R. , Mustafa S. Jamal
Published: December 2008

We hypothesize that A2Aadenosine receptors (A2AAR) promote aortic relaxation in mice through cytochrome P450 (CYP)-epoxygenases and help to avoid salt sensitivity. Aortas from male mice maintained on a high-salt (HS; 7% NaCl) or normal-salt (NS; 0.45% NaCl) diet for 4–5 wks were used. Concentration-response curves (10−11–10−5M) for 5′- N-ethylcarboxamidoadenosine (NECA; a nonselective adenosine analog) and CGS 21680 (A2AAR agonist) were obtained with different antagonists including ZM 241385 (A2AAR antagonist; 10−6M), SCH 58261 (A2AAR antagonist; 10−6M), Nω-nitro-l-arginine methyl ester (l-NAME; endothelial nitric oxide synthase inhibitor; 10−4M) and inhibitors including methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; CYP epoxygenases inhibitor; 10−5M), 14,15-epoxyeicosa-5(z)-enoic acid (14,15-EEZE; EET antagonist; 10−5M), dibromo-dodecenyl-methylsulfimide (DDMS; CYP4A inhibitor; 10−5M), and HET0016 (20-HETE inhibitor; 10−5M). At 10−7M of NECA, significant relaxation in HS (+22.58 ± 3.12%) was observed compared with contraction in NS (−10.62 ± 6.27%, P < 0.05). ZM 241385 changed the NECA response to contraction ( P < 0.05) in HS. At 10−7M of CGS 21680, significant relaxation in HS (+32.04 ± 3.08%) was observed compared with NS (+10.45 ± 1.34%, P < 0.05). SCH 58261, l-NAME, MS-PPOH, and 14,15-EEZE changed the CGS 21680-induced relaxation to contraction ( P < 0.05) in HS. Interestingly, DDMS and HET0016 changed CGS 21680 response to relaxation ( P < 0.05) in NS; however, there was no significant difference found between DDMS, HET0016-treated HS and NS vs. nontreated HS group ( P > 0.05). CYP2C29 protein was 55% and 74% upregulated in HS vs. NS ( P < 0.05) mice aorta and kidney, respectively. CYP4A protein was 30.30% and 35.70% upregulated in NS vs. HS ( P < 0.05) mice aorta and kidneys, respectively. A1AR was downregulated, whereas A2AAR was upregulated in HS compared with NS. These data suggest that HS may activate CYP2C29 via A2AAR, causing relaxation, whereas NS may contribute to the upregulation of CYP4A causing contraction.
Mechanisms of Group I mGluR-Dependent Long-Term Depression of NMDA Receptor–Mediated Transmission at Schaffer Collateral–CA1 Synapses
Authors: Ireland David R. , Abraham Wickliffe C.
Published: December 2008

The mechanisms underlying group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) of N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic currents (EPSCsNMDAR) are poorly understood. Here we investigated the effects of ( R,S)-3,5-dihydroxyphenylglycine (DHPG), a selective agonist of group I mGluRs, on the EPSCsNMDAR in area CA1 of acute hippocampal slices from 6- to 8-wk Sprague-Dawley rats. DHPG acutely and persistently depressed the isolated EPSCNMDAR and transiently slowed its decay rate. Combined antagonism of mGluR1 and mGluR5 blocked the effects of DHPG. Strong calcium buffering with intracellular BAPTA did not reduce the acute depression or LTD, making the involvement of elevated postsynaptic calcium unlikely. The acute depression and LTD were not mediated by activation of tyrosine kinases or phosphatases, nor were they dependent on protein synthesis. However, the LTD was prevented by the intracellular actin-stabilizer jasplakinolide, raising the possibility that it was associated with a lateral movement of NMDARs. Supporting this hypothesis, when the effective spatial spread of synaptically released glutamate was increased using the glutamate transporter inhibitor TBOA, the resultant EPSCNMDAR did not undergo LTD in response to DHPG. Importantly, isolation of the extrasynaptic EPSCNMDAR by blockade of synaptic NMDARs with MK-801 showed that this was not due to a potentiation of the preexisting extrasynaptic component. These findings indicate that LTD of NMDAR-mediated synaptic transmission occurs via lateral movement of receptors away from the synapse.
Whisking in Air: Encoding of Kinematics by Trigeminal Ganglion Neurons in Awake Rats
Authors: Khatri V. , Bermejo R. , Brumberg J. C. , Keller A. , Zeigler H. P.
Published: December 2008

Active sensing requires the brain to distinguish signals produced by external inputs from those generated by the animal's own movements. Because the rodent whisker musculature lacks proprioceptors, we asked whether trigeminal ganglion neurons encode the kinematics of the rat's own whisker movements in air. By examining the role of kinematics, we have extended previous findings showing that many neurons that respond during such movements do not do so consistently. Nevertheless, the majority (∼70%) of trigeminal ganglion neurons display significant correlations between firing rate and a kinematic parameter, and a subset, ∼30%, represent kinematics with high reliability. Preferential firing to movement direction was observed but was strongly modulated by movement amplitude and speed. However, in contrast to the precise time-locking that occurs in response to active whisker contacts, whisker movements in air generate temporally dispersed responses that are not time-locked to the onset of either protractions or retractions.
Near Optimal Combination of Sensory and Motor Uncertainty in Time During a Naturalistic Perception-Action Task
Authors: Faisal A. Aldo , Wolpert Daniel M.
Published: December 2008

Most behavioral tasks have time constraints for successful completion, such as catching a ball in flight. Many of these tasks require trading off the time allocated to perception and action, especially when only one of the two is possible at any time. In general, the longer we perceive, the smaller the uncertainty in perceptual estimates. However, a longer perception phase leaves less time for action, which results in less precise movements. Here we examine subjects catching a virtual ball. Critically, as soon as subjects began to move, the ball became invisible. We study how subjects trade-off sensory and movement uncertainty by deciding when to initiate their actions. We formulate this task in a probabilistic framework and show that subjects' decisions when to start moving are statistically near optimal given their individual sensory and motor uncertainties. Moreover, we accurately predict individual subject's task performance. Thus we show that subjects in a natural task are quantitatively aware of how sensory and motor variability depend on time and act so as to minimize overall task variability.
Temporal Precision of Neuronal Information in a Rapid Perceptual Judgment
Authors: Ghose Geoffrey M. , Harrison Ian T.
Published: December 2008

In many situations, such as pedestrians crossing a busy street or prey evading predators, rapid decisions based on limited perceptual information are critical for survival. The brevity of these perceptual judgments constrains how neuronal signals are integrated or pooled over time because the underlying sequence of processes, from sensation to perceptual evaluation to motor planning and execution, all occur within several hundred milliseconds. Because most previous physiological studies of these processes have relied on tasks requiring considerably longer temporal integration, the neuronal basis of such rapid decisions remains largely unexplored. In this study, we examine the temporal precision of neuronal activity associated with a rapid perceptual judgment. We find that the activity of individual neurons over tens of milliseconds can reliably convey information about sensory events and was well correlated with the animals' judgments. There was a strong correlation between sensory reliability and the correlation with behavioral choice, suggesting that rapid decisions were preferentially based on the most reliable sensory signals. We also find that a simple model in which the responses of a small number of individual neurons (<5) are summed can completely explain behavioral performance. These results suggest that neuronal circuits are sufficiently precise to allow for cognitive decisions to be based on small numbers of action potentials from highly reliable neurons.
Prediction of Subjective Affective State From Brain Activations
Authors: Rolls Edmund T. , Grabenhorst Fabian , Franco Leonardo
Published: December 2008

Decoding and information theoretic techniques were used to analyze the predictions that can be made from functional magnetic resonance neuroimaging data on individual trials. The subjective pleasantness produced by warm and cold applied to the hand could be predicted on single trials with typically in the range 60–80% correct from the activations of groups of voxels in the orbitofrontal and medial prefrontal cortex and pregenual cingulate cortex, and the information available was typically in the range 0.1–0.2 (with a maximum of 0.6) bits. The prediction was typically a little better with multiple voxels than with one voxel, and the information increased sublinearly with the number of voxels up to typically seven voxels. Thus the information from different voxels was not independent, and there was considerable redundancy across voxels. This redundancy was present even when the voxels were from different brain areas. The pairwise stimulus-dependent correlations between voxels, reflecting higher-order interactions, did not encode significant information. For comparison, the activity of a single neuron in the orbitofrontal cortex can predict with 90% correct and encode 0.5 bits of information about whether an affectively positive or negative visual stimulus has been shown, and the information encoded by small numbers of neurons is typically independent. In contrast, the activation of a 3 × 3 × 3-mm voxel reflects the activity of ∼0.8 million neurons or their synaptic inputs and is not part of the information encoding used by the brain, thus providing a relatively poor readout of information compared with that available from small populations of neurons.
Numerical Simulation of the Field Velocities and Local Disturbances of a Long Gravity Wave Passing above an Immersed Vertical Barrier
Authors: Abdelhamid Laouar , Allaoua Guerziz
Published: December 2008

This work is interested in the study of the passage of a long gravity wave above an immersed vertical barrier. The latter is placed at a right angle in the middle of the occupied fluid domain which is limited vertically by both a free surface and an impermeable horizontal bottom. We want to determine the field velocity and the local disturbances in the vicinity of the barrier. For this, we use the generalized theory of shallow water and complex variables method. For illustration, we consider a solitary wave as an emitted long wave.
Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells
Authors: Seo Makoto , Inoue Ikuo , Ikeda Masaaki , Nakano Takanari , Takahashi Seiichiro , Katayama Shigehiro , Komoda Tsugikazu
Published: December 2008

Statins increase peroxisome proliferator‐activated receptor α (PPARα) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose‐dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin‐induced HNF‐4α. (2) PPARα mRNA expression was increased by statin treatment. (3) The PPARα levels in nuclear fractions were increased by statin treatment. (4) Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl‐coenzyme A oxidase promoter and PPARα/RXRα expression vectors. In summary, these data demonstrate that PPARα production and activation are upregulated through the PPARα promoter activity by statin treatment.
Convergence Theorems for Common Fixed Points of Nonself Asymptotically Quasi-Non-Expansive Mappings
Authors: Wang Chao , Zhu Jinghao
Published: December 2008

We introduce a new three-step iterative scheme with errors. Several convergence theorems of this scheme are established for common fixed points of nonself asymptotically quasi-non-expansive mappings in real uniformly convex Banach spaces. Our theorems improve and generalize recent known results in the literature.
A Pathway Analysis Tool for Analyzing Microarray Data of Species with Low Physiological Information
Authors: te Pas M. F. W. , van Hemert S. , Hulsegge B. , Hoekman A. J. W. , Pool M. H. , Rebel J. M. J. , Smits M. A.
Published: December 2008

Pathway information provides insight into the biological processes underlying microarray data. Pathway information is widely available for humans and laboratory animals in databases through the internet, but less for other species, for example, livestock. Many software packages use species‐specific gene IDs that cannot handle genomics data from other species. We developed a species‐independent method to search pathways databases to analyse microarray data. Three PERL scripts were developed that use the names of the genes on the microarray. (1) Add synonyms of gene names by searching the Gene Ontology (GO) database. (2) Search the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database for pathway information using this GO‐enriched gene list. (3) Combine the pathway data with the microarray data and visualize the results using color codes indicating regulation. To demonstrate the power of the method, we used a previously reported chicken microarray experiment investigating line‐specific reactions to Salmonella infection as an example.
Characterization of a Novel Polymorphism in PPARG Regulatory Region Associated with Type 2 Diabetes and Diabetic Retinopathy in Italy
Authors: Costa Valerio , Casamassimi Amelia , Esposito Katherine , Villani Angela , Capone Mariaelena , Iannella Rosa , Schisano Bruno , Ciotola Miryam , Di Palo Carmen , Capone Corrado Feliciantonia , Santangelo Franco , Giugliano Dario , Ciccodicola Alfredo
Published: December 2008

Peroxisome proliferator‐activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C‐2821T polymorphisms, and for a newly identified polymorphism (A‐2819G). The above‐mentioned polymorphisms were analyzed by gene‐specific PCR and direct sequencing of all samples. A significant difference was found for ‐2819G frequency when patients with type 2 diabetes—particularly diabetic women with the proliferative retinopathy—were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A‐2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not.
Outcome of Treatment of Anterior Vaginal Wall Prolapse and Stress Urinary Incontinence with Transobturator Tension-Free Vaginal Mesh (Prolift) and Concomitant Tension-Free Vaginal Tape-Obturator
Authors: Abou-Elela Ashraf , Salah Essam , Torky Haitham , Azazy Sameh
Published: December 2008

Objective. It is to assess the feasibility, effectiveness, and safety of transobturator tension-free vaginal mesh (Prolift) and concomitant tension-free vaginal tape-obturator (TVT-O) system as a treatment of female anterior vaginal wall prolapse associated with stress urinary incontinence (SUI).Patients and Methods. Between December 2006 and July 2007, 20 patients with anterior genital prolapse and voiding dysfunction were treated with the transobturator tension-free vaginal mesh (Prolift) and concomitant tension-free vaginal tape-obturator (TVT-O). Sixteen patients had stress urinary incontinence and 4 patients were considered at risk for development of de novo stress incontinence after the prolapse is repaired. All patients underwent a complete urodynamic assessment. All the patients underwent pelvic examination 4–6 weeks after the operation, and anatomical and functional outcomes were recorded.Results. Twenty cystocoeles were repaired: 6 grade II, 12 grade III, and 2 grade IV. There were no vessel or bladder injuries. Eighteen patients had optimal anatomic results and 2 patients had persistent asymptomatic stage I prolapse.Conclusion. These preliminary results suggest that Prolift system offers a safe and effective treatment for female anterior vaginal wall prolapse. However, a long-term followup is necessary in order to support the good result maintenance.
X-Ray Photoemission Study of the Oxidation of Hafnium
Authors: Chourasia A. R. , Hickman J. L. , Miller R. L. , Nixon G. A. , Seabolt M. A.
Published: December 2008

About 20 Å of hafnium were deposited on silicon substrates using the electron beam evaporation technique. Two types of samples were investigated. In one type, the substrate was kept at the ambient temperature. After the deposition, the substrate temperature was increased to 100, 200, and 300∘C. In the other type, the substrate temperature was held fixed at some value during the deposition. For this type, the substrate temperatures used were 100, 200, 300, 400, 500, 550, and 600∘C. The samples were characterized in situ by the technique of X-ray photoelectron spectroscopy. No trace of elemental hafnium is observed in the deposited overlayer. Also, there is no evidence of any chemical reactivity between the overlayer and the silicon substrate over the temperature range used. The hafnium overlayer shows a mixture of the dioxide and the suboxide. The ratio of the suboxide to dioxide is observed to be more in the first type of samples. The spectral data indicate that hafnium has a strong affinity for oxygen. The overlayer gets completely oxidized to form HfO2 at substrate temperature around 300∘C for the first type of samples and at substrate temperature greater than 550∘C for the second type.
Measurement and Simulation of Pollutant Emissions from Marine Diesel Combustion Engine and Their Reduction by Ammonia Injection
Authors: Larbi Nader , Bessrour Jamel
Published: December 2008

Taking into account the complexity and cost of a direct experimental approach, the recourse to a tool of simulation, which can also predict inaccessible information by measurement, offers an effective and fast alternative to apprehend the problem of pollutant emissions from internal combustion engines. An analytical model based on detailed chemical kinetics employed to calculate the pollutant emissions of a marine diesel engine gave satisfactory results, in general, compared to experimentally measured results. Especially the NO emission values are found to be higher than the limiting values tolerated by the International Maritime Organization (IMO). Thus, this study is undertaken in order to reduce these emissions to the maximum level. The reduction of pollutant emissions is apprehended with ammonia injection.
A Rare Cause for Cervical Pain: Eagle's Syndrome
Authors: Politi Massimo , Toro Corrado , Tenani Giulia
Published: December 2008

Patients with pharyngodynia and neck pain symptoms can lead to an extensive differential diagnosis. Eagle's syndrome must be taken in account. Eagle defined “stylalgia” as an autonomous entity related to abnormal length of the styloid process or to mineralization of the stylohyoid ligament complex. The stylohyoid complex derives from Reichert's cartilage of the second branchial arch. The styloyd process is an elongated conical projection of the temporal bone that lies anteriorly to the mastoid process. The incidence of Eagle's syndrome varies among population. Usually asymptomatic, it occurs in adult patients. It is characterized by pharyngodynia localized in the tonsillar fossa and sometimes accompanied by disphagia, odynophagia, foreign body sensation, and temporary voice changes. In some cases, the stylohyoid apparatus compresses the internal and/or the external carotid arteries and their perivascular sympathetic fibers, resulting in a persistent pain irradiating in the carotid territory. The pathogenesis of the syndrome is still under discussion.
Poly(hydridocarbyne) as Highly Processable Insulating Polymer Precursor to Micro/Nanostructures and Graphite Conductors
Authors: Katzenmeyer Aaron M. , Bayam Yavuz , VJ Logeeswaran , Pitcher Michael W. , Nur Yusuf , Seyyidoğlu Semih , Toppare Levent K. , Talin A. Alec , Han Huilan , Davis Cristina E. , Islam M. Saif
Published: December 2008

Carbon‐based electronic materials have received much attention since the discovery and elucidation of the properties of the nanotube, fullerene allotropes, and conducting polymers. Amorphous carbon, graphite, graphene, and diamond have also been the topics of intensive research. In accordance with this interest, we herein provide the details of a novel and facile method for synthesis of poly(hydridocarbyne) (PHC), a preceramic carbon polymer reported to undergo a conversion to diamond‐like carbon (DLC) upon pyrolysis and also provide electrical characterization after low‐temperature processing and pyrolysis of this material. The results indicate that the strongly insulating polymer becomes notably conductive in bulk form upon heating and contains interspersed micro‐ and nanostructures, which are the subject of ongoing research.
Cusp Fracture Resistance of Maxillary Premolars Restored with the Bonded Amalgam Technique Using Various Luting Agents
Authors: Marchan Shivaughn M. , Coldero Larry , White Daniel , Smith William A. J. , Rafeek Reisha N.
Published: December 2008

Objective. This in vitro study uses measurements of fracture resistance to compare maxillary premolars restored with the bonded amalgam technique using a new resin luting cement, glass ionomer, and resin-modified glass ionomer as the bonding agents.Materials. Eighty-five sound maxillary premolars were selected and randomly assigned to one of five test groups of 17 teeth each. One group of intact teeth served as the control. The remaining groups were prepared to a standard cavity form relative to the dimensions of the overall tooth and restored with amalgam alone or a bonded amalgam using one of three luting agents: RelyX Arc (a new resin luting cement), RelyX luting (a resin-modified glass ionomer), or Ketac-Cemμ(a glass ionomer) as the bonding agents. Each tooth was then subjected to compressive testing until catastrophic failure occurred. The mean loads at failure of each group were statistically compared using ANOVA with a post hoc Bonferroni test.Results. It was found that regardless of the luting cement used for the amalgam bonding technique, there was little effect on the fracture resistance of teeth.Conclusion. Cusp fracture resistance of premolars prepared with conservative MOD cavity preparations is not improved by using an amalgam-bonding technique compared to similar cavities restored with amalgam alone.
MRI Biomarkers of Vascular Damage and Atrophy Predicting Mortality in a Memory Clinic Population
Authors: Henneman Wouter J.P. , Sluimer Jasper D. , Cordonnier Charlotte , Baak Merel M.E. , Scheltens Philip , Barkhof Frederik , van der Flier Wiesje M.
Published: December 2008

Background and Purpose—

MRI biomarkers play an important role in the diagnostic work-up of dementia, but their prognostic value is less well-understood. We investigated if simple MRI rating scales predict mortality in a memory clinic population.

Methods—

We included 1138 consecutive patients attending our memory clinic. Diagnostic categories were: subjective complaints (n=220), mild cognitive impairment (n=160), Alzheimer disease (n=357), vascular dementia (n=46), other dementia (n=136), and other diagnosis (n=219). Baseline MRIs were assessed using visual rating scales for medial temporal lobe atrophy (range, 0–4), global cortical atrophy (range, 0–3), and white matter hyperintensities (range, 0–3). Number of microbleeds and presence of infarcts were recorded. Cox-regression models were used to calculate the risk of mortality.

Results—

Mean follow-up duration was 2.6 (±1.9) years. In unadjusted models, all MRI markers except infarcts predicted mortality. After adjustment for age, sex, and diagnosis, white matter hyperintensities, and microbleeds predicted mortality (white matter hyperintensities: hazard ratio [HR], 1.2; 95% CI, 1.0–1.4; microbleeds: HR, 1.02 95% CI, 1.00–1.03; categorized: HR, 1.5; 95% CI, 1.1–2.0). The predictive effect of global cortical atrophy was restricted to younger subjects (HR, 1.7; 95% CI, 1.2–2.6). An interaction between microbleeds and global cortical atrophy indicated that mortality was especially high in patients with both microbleeds and global cortical atrophy.

Conclusion—

Simple MRI biomarkers, in addition to their diagnostic use, have a prognostic value with respect to mortality in a memory clinic population. Microbleeds were the strongest predictor of mortality.
Recanalization of Spontaneous Carotid Artery Dissection
Authors: Nedeltchev Krassen , Bickel Stefan , Arnold Marcel , Sarikaya Hakan , Georgiadis Dimitrios , Sturzenegger Matthias , Mattle Heinrich P. , Baumgartner Ralf W.
Published: December 2008

Background and Purpose—We set out to investigate the predictors and time course for recanalization of spontaneous dissection of the cervical internal carotid artery (SICAD).

Methods—We prospectively included 249 consecutive patients (mean age, 45±11 years) with 268 SICAD. Ultrasound examinations were performed at presentation, during the first month, and then at 3, 6, and 12 months, and clinical follow-ups after 3, 6, and 12 months.

Results—Of 268 SICADs, 20 (7.5%) presented with ≤50% stenosis, 31 (11.6%) with 51% to 80% stenosis, 92 (34.3%) with 81% to 99% stenosis, and 125 (46.6%) with an occlusion. Antithrombotic treatment included anticoagulation in 174 (67%) patients, aspirin in 64 (24%) patients, and aspirin followed by anticoagulation or vice versa in 22 (8%) patients. Follow-up ultrasound showed normal findings in 160 (60%), ≤50% stenosis in 27 (10%), 51% to 80% stenosis in 4 (1%), 81% to 99% stenosis in 26 (10%), and occlusion in 51 (19%) vessels. The rate of complete recanalization was 16% at 1 month, 50% at 3 months, and 60% at 6 and 12 months. Initial occlusion of the dissected vessels reduced the odds of recanalization (OR, 4.0; 95% CI, 2.2–7.3;P<0.001), whereas the occurrence of local symptoms and signs only at presentation were independently associated with complete recanalization (OR, 0.4; 95% CI, 0.2–0.8;P=0.048).

Conclusions—These results suggest that recanalization of SICAD occurs mainly within the first 6 months after the onset of symptoms. Initial occlusion reduces the likelihood of complete recanalization, whereas presentation with local symptoms and signs only increases it.
Clinical Prediction of Functional Outcome After Ischemic Stroke
Authors: Kissela Brett , Lindsell Christopher J. , Kleindorfer Dawn , Alwell Kathleen , Moomaw Charles J. , Woo Daniel , Flaherty Matthew L. , Air Ellen , Broderick Joseph , Tsevat Joel
Published: December 2008

Background and Purpose—

We sought to build models that address questions of interest to patients and families by predicting short- and long-term mortality and functional outcome after ischemic stroke, while allowing for risk restratification as comorbid events accumulate.

Methods—

A cohort of 451 ischemic stroke subjects in 1999 were interviewed during hospitalization, at 3 months, and at approximately 4 years. Medical records from the acute hospitalization were abstracted. All hospitalizations for 3 months poststroke were reviewed to ascertain medical and psychiatric comorbidities, which were categorized for analysis. Multivariable models were derived to predict mortality and functional outcome (modified Rankin Scale) at 3 months and 4 years. Comorbidities were included as modifiers of the 3-month models, and included in 4-year predictions.

Results—

Poststroke medical and psychiatric comorbidities significantly increased short-term poststroke mortality and morbidity. Severe periventricular white matter disease (PVWMD) was significantly associated with poor functional outcome at 3 months, independent of other factors, such as diabetes and age; inclusion of this imaging variable eliminated other traditional risk factors often found in stroke outcomes models. Outcome at 3 months was a significant predictor of long-term mortality and functional outcome. Black race was a predictor of 4-year mortality.

Conclusions—

We propose that predictive models for stroke outcome, as well as analysis of clinical trials, should include adjustment for comorbid conditions. The effects of PVWMD on short-term functional outcomes and black race on long-term mortality are findings that require confirmation.
Optimal Tmax Threshold for Predicting Penumbral Tissue in Acute Stroke
Authors: Olivot Jean-Marc , Mlynash Michael , Thijs Vincent N. , Kemp Stephanie , Lansberg Maarten G. , Wechsler Lawrence , Bammer Roland , Marks Michael P. , Albers Gregory W.
Published: December 2008

Background and Purpose—

We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions.

Methods—

DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes.

Results—

Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax >4 seconds threshold provided a more accurate prediction of final infarct volume than the >2 seconds threshold.

Conclusions—

Defining PWI lesions based on a stricter Tmax threshold than the standard >2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.
Association Between Gait Asymmetry and Brain Lesion Location in Stroke Patients
Authors: Alexander Lisa D. , Black Sandra E. , Patterson Kara K. , Gao Fuqiang , Danells Cynthia J. , McIlroy William E.
Published: December 2008

Background and Purpose—

Associations between the site of brain injury and poststroke gait impairment are poorly understood. Temporal gait asymmetry after stroke is a salient index of gait dysfunction that has important functional consequences. The current study investigated whether subtraction lesion analysis could distinguish brain regions associated with persisting temporal gait asymmetry in chronic stroke patients.

Methods—

Analysis was conducted on 37 chronic ambulatory stroke patients (17 symmetrical gait, 20 asymmetrical gait). Spatiotemporal gait parameters were recorded using an instrumented walking surface. Lesions were traced from 3D T1-MRI, and region of interest images were generated. The lesion overlay of patients with symmetrical gait was subtracted from patients with asymmetrical gait to highlight voxels more frequently lesioned in asymmetrical patients and relatively spared in symmetrical patients.

Results—

Demographic data were comparable between the 2 groups. Asymmetrical patients exhibited significantly higher National Institute of Health Stroke Scale neglect scores and more severe motor impairment. Gait asymmetry was significantly correlated to Chedoke-McMaster Stroke Scale leg (
r
=−0.767,
P
<0.001) and foot (
r
=−0.759,
P
<0.001) scores, whereas gait speed correlated less strongly. After subtraction analysis, injury to the posterolateral putamen was evident 60% to 80% more frequently in the asymmetrical group compared to the symmetrical group.

Conclusions—

In this sample of ambulatory chronic stroke patients, damage to the posterolateral putamen was associated with temporal gait asymmetry. Further advances in our understanding of the neural correlates of gait asymmetry may provide prognostic markers for future persistent gait dysfunction and lead to early targeted rehabilitation when key regions are damaged.
Association Between Recent Sports Activity, Sports Activity in Young Adulthood, and Stroke
Authors: Grau Armin J. , Barth Cordula , Geletneky Beate , Ling Paul , Palm Frederik , Lichy Christoph , Becher Heiko , Buggle Florian
Published: December 2008

Background and Purpose—

Leisure-time physical activity protects from stroke. It is insufficiently established whether early lifetime physical activity is independently protective and whether some etiologic stroke subgroups particularly benefit from physical activity. We tested the hypothesis that both recent and early-adulthood sports activities are associated with reduced odds of stroke and analyzed their effects in stroke subtypes.

Methods—

We performed a case-control study of 370 patients with acute stroke or transient ischemic attack (TIA) and 370 age- and sex-matched control subjects randomly selected from the population and assessed recent and young adulthood sports activities and their weekly duration in standardized interviews.

Results—

Recent regular sports activities were less often reported by patients (94/370, 25.4%) than by control subjects (162/370, 43.8%;
P
<0.0001). After adjustment for vascular risk factors, education, and other factors, recent participation in sports was significantly associated with reduced odds of stroke/TIA (odds ratio=0.64; 95% CI, 0.43 to 0.96). Both groups did not differ with regard to sports activities in young adulthood. More control subjects (69/365, 18.9%) than patients (25/361, 6.9%) participated in sports recently after not having been active in young adulthood, and such a pattern was associated with reduced odds of stroke/TIA in multivariable analysis (odds ratio=0.37; 95% CI, 0.21 to 0.85).

Conclusions—

Our study supports previous results that have shown stroke protection by physical activity. Results suggest that continuous lifetime activity or starting activities during later adulthood is required to reduce stroke risk.
Arm Use After Left or Right Hemiparesis Is Influenced by Hand Preference
Authors: Rinehart Jenny K. , Singleton Rena D. , Adair John C. , Sadek Joseph R. , Haaland Kathleen Y.
Published: December 2008

Background and Purpose—

Despite strong evidence for hand preference and its impact on motor performance, its influence on stroke rehabilitation has not been routinely considered. Previous research demonstrates that patients with hemiparetic stroke use their ipsilesional, nonparetic arm 5 to 6 times more frequently than their paretic arm, but it is unknown if such use varies with laterality of hemiparesis. The purpose of our study was to determine if the right arm is used more frequently in right-handed patients with stroke.

Methods—

We assessed relative use of the right, left, and both arms with wrist accelerometers on patients with unilateral, paretic stroke matched for degree of paresis (12 with right hemisphere damage, 17 with left hemisphere damage) and 25 neurologically intact control participants as they performed the Arm Motor Ability Test.

Results—

We showed: (1) ipsilesional arm use was greater after right hemisphere damage than left hemisphere damage; (2) the left hemisphere damage group used both arms together more often than the right hemisphere damage group but less often than the control group; and (3) both stroke groups used their contralesional, paretic arm to the same degree.

Conclusions—

These findings emphasize the influence of hand preference on arm use after stroke for the ipsilesional but not the contralesional arm. Although both stroke groups used their ipsilesional more than their contralesional arm, the difference was greater for the right hemisphere damage group who used their ipsilesional arm 4 times more frequently than their contralesional arm, whereas the left hemisphere damage group used their ipsilesional arm 2 times more frequently than their contralesional arm.
Modified Constraint-Induced Therapy Combined With Mental Practice
Authors: Page Stephen J. , Levine Peter , Khoury Jane C.
Published: December 2008

Background and Purpose—

Modified constraint-induced therapy (mCIT) is an outpatient therapy encouraging repetitive, task-specific practice with the affected arm. mCIT has shown efficacy in all stages poststroke. Given its efficacy when combined with other therapy regimens, the current study examined the efficacy of mental practice when combined with mCIT versus mCIT only using randomized, controlled methods.

Method—

Ten patients with chronic stroke (7 males; mean age, 61.4±3.02 years; age range, 48 to 79 years; mean time since stroke, 28.5 months; range, 13 to 42 months) exhibiting stable, affected arm motor deficits were administered mCIT, consisting of: (1) structured therapy emphasizing affected arm use in functional activities 3 days/week for 10 weeks; and (2) less affected arm restraint 5 days/week for 5 hours. Both of these components were administered during a 10-week period. Subjects randomly assigned to the mCIT+mental practice experimental condition also received 30-minute mental practice sessions provided directly after therapy sessions. These mental practice sessions required daily cognitive rehearsal of the activities of daily living practiced during mCIT clinical sessions.

Results—

No pre-existing differences were found between groups on any demographic variable or movement scale. All subjects exhibited marked reductions in affected arm impairment and functional limitation. However, subjects in the mCIT+mental practice group exhibited significantly larger changes on both movement measures after intervention: Action Research Arm Test, +15.4-point change versus +8.4-point change for mCIT only subjects (
P
<0.001); Fugl-Meyer, +7.8-point change versus +4.1-point change for the mCIT only subjects (
P
=0.01). These changes were sustained 3 months after intervention.

Conclusions—

mCIT remains a promising motor intervention. However, its efficacy appears to be enhanced by use of mental practice provided directly after mCIT clinical sessions.
Microarray RNA Expression Analysis of Cerebral White Matter Lesions Reveals Changes in Multiple Functional Pathways
Authors: Simpson Julie E. , Hosny Ola , Wharton Stephen B. , Heath Paul R. , Holden Hazel , Fernando Malee S. , Matthews Fiona , Forster Gill , O'Brien John T. , Barber Robert , Kalaria Raj N. , Brayne Carol , Shaw Pamela J. , Lewis Claire E. , Ince Paul G.
Published: December 2008

Background and Purpose—

White matter lesions (WML) in brain aging are linked to dementia and depression. Ischemia contributes to their pathogenesis but other mechanisms may contribute. We used RNA microarray analysis with functional pathway grouping as an unbiased approach to investigate evidence for additional pathogenetic mechanisms.

Methods—

WML were identified by MRI and pathology in brains donated to the Medical Research Council Cognitive Function and Ageing Study Cognitive Function and Aging Study. RNA was extracted to compare WML with nonlesional white matter samples from cases with lesions (WM[L]), and from cases with no lesions (WM[C]) using RNA microarray and pathway analysis. Functional pathways were validated for selected genes by quantitative real-time polymerase chain reaction and immunocytochemistry.

Results—

We identified 8 major pathways in which multiple genes showed altered RNA transcription (immune regulation, cell cycle, apoptosis, proteolysis, ion transport, cell structure, electron transport, metabolism) among 502 genes that were differentially expressed in WML compared to WM[C]. In WM[L], 409 genes were altered involving the same pathways. Genes selected to validate this microarray data all showed the expected changes in RNA levels and immunohistochemical expression of protein.

Conclusion—

WML represent areas with a complex molecular phenotype. From this and previous evidence, WML may arise through tissue ischemia but may also reflect the contribution of additional factors like blood–brain barrier dysfunction. Differential expression of genes in WM[L] compared to WM[C] indicate a “field effect” in the seemingly normal surrounding white matter.