bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of hand cooling at reducing exercise-induced hyperthermia and improving distance-race performance in wheelchair and able-bodied athletes
Authors: Goosey-Tolfrey Victoria , Swainson Michelle , Boyd Craig , Atkinson Greg , Tolfrey Keith
Published: April 2008

The purpose of this study was to examine the effectiveness of reducing core temperature in postexercise hyperthermic subjects and to assess if hand cooling (HC) improves subsequent timed distance performance. Following a detailed measurement check on the use of insulated auditory canal temperature (Tac), eight wheelchair (WA) athletes and seven male able-bodied (AB) athletes performed two testing sessions, comprising a 60-min exercise protocol and 10-min recovery period, followed by a performance trial (1 km and 3 km for WA and AB, respectively) at 30.8°C (SD 0.2) and 60.6% (SD 0.2) relative humidity. In a counterbalanced order, HC and a no-cooling condition was administered during the 10-min recovery period before the performance trial. Nonsignificant condition × time interactions for both WA ( F15,75= 1.5, P = 0.14) and AB ( F15,90= 1.2, P = 0.32) confirmed that the exercise-induced changes (Δ) in Tacwere similar before each intervention. However, the exercise-induced increase was evidently greater in AB compared with WA (2.0 vs. 1.3°C change, respectively). HC produced ΔTacof −0.4°C (SD 0.4) and −1.2°C (SD 0.2) in comparison (WA and AB, respectively), and simple-effects analyses suggested that the reductions in Tacwere noteworthy after 4 min of HC. HC had an impact on improving AB performances by −4.0 s (SD 11.5) ( P < 0.05) and WA by −20.5 s (SD 24.2) ( P > 0.05). In conclusion, extraction of heat through the hands was effective in lowering Tacin both groups and improving 3-km performance in the AB athletes and trends toward positive gains for the 1-km performance times of the WA group.
Endogenous and exogenous female sex hormones and renal electrolyte handling: effects of an acute sodium load on plasma volume at rest
Authors: Sims Stacy T. , Rehrer Nancy J. , Bell Melanie L. , Cotter James D.
Published: April 2008

This study was conducted to investigate effects of an acute sodium load on resting plasma volume (PV) and renal mechanisms across the menstrual cycle of endurance-trained women with natural (NAT) or oral contraceptive pill (OCP) controlled cycles. Twelve women were assigned to one of two groups, according to their usage status: 1) OCP [ n = 6, 29 yr (SD 6), 59.4 kg (SD 3.2)], or 2) NAT [ n = 6, 24 yr (SD 5), 61.3 kg (SD 3.6)]. The sodium load was administered as a concentrated sodium chloride/citrate beverage (164 mmol Na+/l, 253 mosmol/kgH2O, 10 ml/kg body mass) during the last high-hormone week of the OCP cycle (OCPhigh) or late luteal phase of the NAT cycle (NAThigh) and during the low-hormone sugar pill week of OCP (OCPlow) or early follicular phase of the NAT cycle (NATlow). The beverage (∼628 ml) was ingested in seven portions across 60 min. Over the next 4 h, PV expanded more in the low-hormone phase for both groups (time-averaged change): OCPlow 6.1% (SD 1.1) and NATlow 5.4% (SD 1.2) vs. OCPhigh 3.9% (SD 0.9) and NAThigh 3.5% (SD 0.8) ( P = 0.02). The arginine vasopressin increased less in the low-hormone phase [1.63 (SD 0.2) and 1.30 pg/ml (SD 0.2) vs. 1.82 (SD 0.3) and 1.57 pg/ml (SD 0.5), P = 0.0001], as did plasma aldosterone concentration (∼64% lower, P = 0.0001). Thus PV increased more and renal hormone sensitivity was decreased in the low-hormone menstrual phase following sodium/fluid ingestion, irrespective of OCP usage.
Sensitizing effects of chronic exposure and acute inhalation of ovalbumin aerosol on pulmonary C fibers in rats
Authors: Zhang Guangfan , Lin Ruei-Lung , Wiggers Michelle E. , Lee Lu-Yuan
Published: April 2008

The effect of ovalbumin (Ova) sensitization on pulmonary C-fiber sensitivity was investigated. Brown-Norway rats were sensitized by intraperitoneal injection of Ova followed by aerosolized Ova three times per week for 3 wk. Control rats received the vehicle. At the end of the third week, single-unit fiber activities (FA) of pulmonary C fibers were recorded in anesthetized, artificially ventilated rats. Our results showed the following: 1) Ova sensitization induced airway inflammation (infiltration of eosinophils and neutrophils) and airway hyperresponsiveness in rats; 2) baseline FA in sensitized rats was significantly higher than that in control ones; 3) similarly, the pulmonary C-fiber response to right atrial injection of capsaicin was markedly higher in sensitized rats, which were significantly amplified after the acute Ova inhalation challenge; and 4) similar patterns, but smaller magnitudes of the differences in C-fiber responses to adenosine and lung inflation, were also found between sensitized and control rats. In conclusion, Ova sensitization elevated the baseline FA and excitability of pulmonary C fibers, and the hypersensitivity was further potentiated after the acute Ova inhalation challenge in sensitized rats. Chronic allergic inflammatory reactions in the airway probably contributed to the sensitizing effect on these lung afferents.
Reweighting Sensory Signals to Maintain Head Stability: Adaptive Properties of the Cervicocollic Reflex
Authors: Reynolds J. S. , Blum D. , Gdowski G. T.
Published: April 2008

A major goal of this study was to characterize the cervicocollic reflexes (CCRs) in awake squirrel monkeys and compare it to observations in cat. This was carried out by stabilizing the head in space while rotating the lower body. The magnitude and phase of the torque produced between the head and the restraint system was used as an indicator of the CCR. Many properties of the squirrel monkey's CCR were found to be similar to those of the cat. The torque decreased as a function of frequency and amplitude. In addition, the static level of torque increased with head eccentricity. One difference was that the torque was 90× smaller in squirrel monkeys. Biomechanical differences, such as differences in head inertia, could account for these differences. The second goal was to determine if the CCR was sensitive to increases in the head's inertia. To test this, we increased the head's inertia by a factor of 36 and allowed the reflexes to adapt by rotating the whole body while the head was free to move. The CCR was rapidly assessed by periodically stabilizing the head in space during whole-body rotations. The magnitude of the torque increased by nearly 60%, suggesting that the CCR may adapt when changes in the head's inertia are imposed. Changes in the torque were also consistent with changes in head-movement kinematics during whole-body rotation. This suggests that the collic reflexes may dynamically adapt to maintain the performance and kinematics of reflexive head movement.
Interaction Between Developing Spinal Locomotor Networks in the Neonatal Mouse
Authors: Gordon Ian T. , Dunbar Mary J. , Vanneste Kimberly J. , Whelan Patrick J.
Published: April 2008

At birth, thoracosacral spinal cord networks in mouse can produce a coordinated locomotor-like pattern. In contrast, less is known about the cervicothoracic networks that generate forelimb locomotion. Here we show that cervical networks can produce coordinated rhythmic patterns in the brain stem-spinal cord preparation of the mouse. Segmentally the C5 and C8 neurograms were each found to be alternating left-right, and the ipsilateral C5 and C8 neurograms also alternated. Collectively these patterns were suggestive of locomotor-like activity. This pattern was not dependent on the presence of thoracosacral segments because they could be evoked following a complete transection of the spinal cord at T5. We next demonstrated that activation of thoracosacral networks either pharmacologically or by stimulation of sacrocaudal afferents could produce rhythmic activity within the C5 and C8 neurograms. On the other hand, pharmacological activation of cervical networks did not evoke alternating cervical rhythmic activity either in isolated cervicothoracic or -sacral preparations. Under these conditions, we found that activation of cervicothoracic networks could alter the timing of thoracosacral locomotor-like patterns. When thoracosacral networks were not activated pharmacologically but received rhythmic drive from cervicothoracic networks, a pattern of slow bursts with superimposed fast synchronous oscillations became the dominant lumbar neurogram pattern. Our data suggest that in neonatal mice the cervical CPG is capable of producing coordinated rhythmic patterns in the absence of input from lumbar segments, but caudorostral drive contributes to cervical patterns and rhythm stability.
Probability-Based Prediction of Activity in Multiple Arm Muscles: Implications for Functional Electrical Stimulation
Authors: Anderson Chad V. , Fuglevand Andrew J.
Published: April 2008

Functional electrical stimulation (FES) involves artificial activation of muscles with implanted electrodes to restore motor function in paralyzed individuals. The range of motor behaviors that can be generated by FES, however, is limited to a small set of preprogrammed movements such as hand grasp and release. A broader range of movements has not been implemented because of the substantial difficulty associated with identifying the patterns of muscle stimulation needed to elicit specified movements. To overcome this limitation in controlling FES systems, we used probabilistic methods to estimate the levels of muscle activity in the human arm during a wide range of free movements based on kinematic information of the upper limb. Conditional probability distributions were generated based on hand kinematics and associated surface electromyographic (EMG) signals from 12 arm muscles recorded during a training task involving random movements of the arm in one subject. These distributions were then used to predict in four other subjects the patterns of muscle activity associated with eight different movement tasks. On average, about 40% of the variance in the actual EMG signals could be accounted for in the predicted EMG signals. These results suggest that probabilistic methods ultimately might be used to predict the patterns of muscle stimulation needed to produce a wide array of desired movements in paralyzed individuals with FES.
Development of Presynaptic Inhibition Onto Retinal Bipolar Cell Axon Terminals Is Subclass-Specific
Authors: Schubert Timm , Kerschensteiner Daniel , Eggers Erika D. , Misgeld Thomas , Kerschensteiner Martin , Lichtman Jeff W. , Lukasiewicz Peter D. , Wong Rachel O. L.
Published: April 2008

Synaptic integration is modulated by inhibition onto the dendrites of postsynaptic cells. However, presynaptic inhibition at axonal terminals also plays a critical role in the regulation of neurotransmission. In contrast to the development of inhibitory synapses onto dendrites, GABAergic/glycinergic synaptogenesis onto axon terminals has not been widely studied. Because retinal bipolar cells receive subclass-specific patterns of GABAergic and glycinergic presynaptic inhibition, they are a good model for studying the development of inhibition at axon terminals. Here, using whole cell recording methods and transgenic mice in which subclasses of retinal bipolar cells are labeled, we determined the temporal sequence and patterning of functional GABAergic and glycinergic input onto the major subclasses of bipolar cells. We found that the maturation of GABAergic and glycinergic synapses onto the axons of rod bipolar cells (RBCs), on-cone bipolar cells (on-CBCs) and off-cone bipolar cells (off-CBCs) were temporally distinct: spontaneous chloride-mediated currents are present in RBCs earlier in development compared with on- and off-CBC, and RBCs receive GABAergic and glycinergic input simultaneously, whereas in off-CBCs, glycinergic transmission emerges before GABAergic transmission. Because on-CBCs show little inhibitory activity, GABAergic and glycinergic events could not be pharmacologically distinguished for these bipolar cells. The balance of GABAergic and glycinergic input that is unique to RBCs and off-CBCs is established shortly after the onset of synapse formation and precedes visual experience. Our data suggest that presynaptic modulation of glutamate transmission from bipolar cells matures rapidly and is differentially coordinated for GABAergic and glycinergic synapses onto distinct bipolar cell subclasses.
Extrapolation of Visual Motion for Manual Interception
Authors: Soechting John F. , Flanders Martha
Published: April 2008

A frequent goal of hand movement is to touch a moving target or to make contact with a stationary object that is in motion relative to the moving head and body. This process requires a prediction of the target's motion, since the initial direction of the hand movement anticipates target motion. This experiment was designed to define the visual motion parameters that are incorporated in this prediction of target motion. On seeing a go signal (a change in target color), human subjects slid the right index finger along a touch-sensitive computer monitor to intercept a target moving along an unseen circular or oval path. The analysis focused on the initial direction of the interception movement, which was found to be influenced by the time required to intercept the target and the target's distance from the finger's starting location. Initial direction also depended on the curvature of the target's trajectory in a manner that suggested that this parameter was underestimated during the process of extrapolation. The pattern of smooth pursuit eye movements suggests that the extrapolation of visual target motion was based on local motion cues around the time of the onset of hand movement, rather than on a cognitive synthesis of the target's pattern of motion.
Gallstone Ileus: Clinical Presentation of a Benign Mechanical Intestinal Obstruction
Authors: Montalvo-Jave Eduardo E. , Alegre-Tamez Eduardo , Athie-Gutiérrez César
Published: April 2008

Gallstone ileus is a rare cause of small bowel obstruction which usually presents in elderly female patients and which has been associated with high morbidity and mortality rates. We present the case of a 63-year-old man who presented at our institution with symptoms of bowel obstruction. Abdominal X-ray and exploratory laparotomy revealed a large gallstone in the terminal ileus.
Optical Coherence Tomography Fast versus Regular Macular Thickness Mapping in Diabetic Retinopathy
Authors: Ceklic Lala , Maár Noémi , Neubauer Aljoscha S.
Published: April 2008

Objective: The purpose of the study was to investigate if absolute values and reproducibility of thickness maps obtained from 2 optical coherence tomography (OCT) scanning protocols, regular high-resolution and fast low-density mode, differ in patients with diabetic macular edema. Methods: A total of 26 consecutive patients undergoing fluorescein angiography and Stratus OCT scanning for the evaluation of diabetic macular edema at the Departments of Ophthalmology in Munich and Vienna were included. Results: Retinal thickness of the central field of the thickness map measured by fast retinal thickness protocol was 287 ± 97 and 290 ± 113 µm by the regular protocol. This difference as well as that for all other fields was not statistically significant. Three times repeated measurements applying both OCT scanning modes in 10 patients yielded very good intrasession correlation coefficients between 0.70 and 0.99, with corresponding intrasession standard deviations ranging between 6 and 16 µm. The fast mode yielded slightly less reproducible values than the regular mode. Visual acuity did not influence the results. Conclusion: In practice both scanning modes can be interchanged and absolute values can be compared directly. Best reproducibility is obtained with higher sampling density even in patients with reduced visual acuity due to diabetic macular edema.
Exposure to the US Stroke Buckle as a Risk Factor for Cerebrovascular Mortality
Authors: Shrira Ilan , Christenfeld Nicholas , Howard George
Published: April 2008

Background: For decades, the Stroke Buckle region in the southeastern USA has had a high incidence of deaths from cerebrovascular disease relative to the rest of the country. We test here the possibility that temporary exposure to the Stroke Buckle can explain some of the excessive stroke mortality there. Methods: We examined all US death records between 1979 and 1988, noting whether individuals died inside or outside the 153-county Stroke Buckle in the coastal plains of North Carolina, South Carolina and Georgia. We also noted the decedents’ county of residence, which was coded separately. Proportionate mortality ratios (PMRs) were used to assess the risk of dying of a stroke. Results: Stroke Buckle residents who died in their home county were at an increased risk of dying of a stroke (PMR = 130.2; 95% confidence interval, CI = 128.9–131.6; p < 0.0001). Visitors to the Buckle were also at an increased risk of dying of a stroke (PMR = 111.9; 95% CI = 107.5–116.2; p < 0.0001), and Buckle residents who died while outside of the region were less likely to die of a stroke (PMR = 89.9; 95% CI = 86.2–93.6; p < 0.0001). Conclusions: These results show that even short-term exposure to the Stroke Buckle accounts for some of the elevation in stroke deaths there.
Commercialization of Kidney Transplants: A Systematic Review of Outcomes in Recipients and Donors
Authors: Sajjad Imran , Baines Lyndsay S. , Patel Prem , Salifu Moro O. , Jindal Rahul M.
Published: April 2008

In this study we systematically reviewed outcomes in recipients and donors of commercial kidney transplants. Inherent in a study of this nature is the possibility of center and country bias, in particular there are no publications from China and South America. Publications also tended to report poor outcomes which may reflect bias on the part of the authors or to highlight the ethical issues in this area. We were unable to perform a meta-analysis due to variability in studies making it impossible to synthesize the data other than descriptive. Furthermore, these studies were not large or well conducted. We found that patient and graft survival was generally inferior to the data obtained from the UNOS (United Network for Organ Sharing). Some studies did achieve good outcomes, however, due to lack of details, it was not possible to infer if the donor hospital, surgical technique or immunosuppressive regimen was a factor. There was a higher incidence of unconventional and life-threatening infections such as malaria, invasive fungal infections, pneumonia, HIV and hepatitis. There was also a markedly increased incidence of postoperative surgical interventions in recipients. We suggest the establishment of a database for both recipients and donors to identify unique surgical, medical, infectious and immunosuppressive protocols for the recipients and donors in these hospitals. This could lead to better liaison between the recipient and donor hospitals so that modern surgical and medical practices can be implemented. There should also be improved emotional and psychological support to both the recipient and the donor. However, these steps could be seen as condoning the reprehensible practice of commercialization of human body parts.
Initial Glucose Load Predicts Technique Survival in Patients on Chronic Peritoneal Dialysis
Authors: Wu Hon-Yen , Hung Kuan-Yu , Huang Jenq-Wen , Chen Yung-Ming , Tsai Tun-Jun , Wu Kwan-Dun
Published: April 2008

Background: A high glucose content in peritoneal dialysis (PD) solution may result in unfavorable changes on peritoneal character and worsened metabolic profiles. We conducted this retrospective cohort analysis to investigate the impact of initial glucose load on long-term outcomes of PD patients. Methods: A total of 90 patients newly started on PD were enrolled. All subjects were divided into low, medium, or high glucose load equally in patient number according to the average dialysate glucose concentration prescribed in the first 6 months from PD initiation. Cox’s regression was used for survival analyses and linear regression was used for analyses of determinants for glucose load. Results: The mean follow-up period was 40.1 ± 11.8 months. Patients with higher glucose load showed a significantly worse cumulative technique survival (log rank p = 0.002). In Cox’s regression analysis, patients with lower glucose load had significantly better technique survival (p = 0.035). In linear regression analysis, preexisting diabetes mellitus (p < 0.001), lower serum albumin (p = 0.012), and lower weekly renal Kt/V (p = 0.019) were significantly correlated with higher glucose load. Conclusions: Higher glucose load during the initial period of PD was associated with higher prevalent diabetes mellitus, lower serum albumin, and lower residual renal function, and effectively predicted worse survival of PD therapy.
Heparin-Binding Epidermal Growth Factor–Like Growth Factor Signaling in Flow-Induced Arterial Remodeling
Authors: Zhang Hua , Sunnarborg Susan W. , McNaughton K. Kirk , Johns Terrance G. , Lee David C. , Faber James E.
Published: April 2008

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is activated by reduced endothelial shear stress and stimulates smooth muscle cell proliferation in vitro. Moreover, HB-EGF is augmented at sites of intimal hyperplasia and atherosclerosis, conditions favored by low/disturbed shear stress. We thus tested whether HB-EGF contributes to low flow-induced negative hypertrophic remodeling (FINR) of a mouse carotid artery. Blood flow was surgically decreased in the left and increased in the right common carotid arteries. After 21 days, the left carotid artery exhibited lumen narrowing, thickening of intima–media and adventitia, and increased circumference that were inhibited by ≈50% in HB-EGF
+/−
and ≈90% in HB-EGF
−/−
mice. FINR was also inhibited by the EGF receptor inhibitor AG1478. In contrast, eutrophic outward remodeling of the right carotid artery was unaffected in HB-EGF
+/−
and HB-EGF
−/−
mice, nor by AG1478. FINR-induced proliferation and leukocyte accumulation were reduced in HB-EGF
−/−
. FINR was associated with increased reactive oxygen species, increased expression of pro-HB-EGF and tumor necrosis factor α–converting enzyme (pro-HB-EGF sheddase), increased phosphorylation of EGF receptor and extracellular signal-regulated kinase 1/2, and increased nuclear factor κB activity. Apocynin and deletion of p47
phox
inhibited FINR, whereas deletion of HB-EGF abolished nuclear factor κB activation in smooth muscle cells. These findings suggest that HB-EGF signaling is required for low flow-induced hypertrophic remodeling and may participate in vascular wall disease and remodeling.
Sex, Age, and Regional Differences in L-Type Calcium Current Are Important Determinants of Arrhythmia Phenotype in Rabbit Hearts With Drug-Induced Long QT Type 2
Authors: Sims Carl , Reisenweber Steven , Viswanathan Prakash C. , Choi Bum-Rak , Walker William H. , Salama Guy
Published: April 2008

In congenital and acquired long QT type 2, women are more vulnerable than men to Torsade de Pointes. In prepubertal rabbits (and children), the arrhythmia phenotype is reversed; however, females still have longer action potential durations than males. Thus, sex differences in K+channels and action potential durations alone cannot account for sex-dependent arrhythmia phenotypes. The L-type calcium current (ICa,L) is another determinant of action potential duration, Ca2+overload, early afterdepolarizations (EADs), and Torsade de Pointes. Therefore, sex, age, and regional differences inICa,Ldensity and in EAD susceptibility were analyzed in epicardial left ventricular myocytes isolated from the apex and base of prepubertal and adult rabbit hearts. In prepubertal rabbits, peakICa,Lat the base was 22% higher in males than females (6.4±0.5 versus 5.0±0.2 pA/pF;P<0.03) and higher than at the apex (6.4±0.5 versus 5.0±0.3 pA/pF;P<0.02). Sex differences were reversed in adults:ICa,Lat the base was 32% higher in females than males (9.5±0.7 versus 6.4±0.6 pA/pF;P<0.002) and 28% higher than the apex (9.5±0.7 versus 6.9±0.5 pA/pF;P<0.01). Apex–base differences inICa,Lwere not significant in adult male and prepubertal female hearts. Western blot analysis showed that Cav1.2α levels varied with sex, maturity, and apex–base, with differences similar to variations inICa,L; optical mapping revealed that the earliest EADs fired at the base. Single myocyte experiments and Luo–Rudy simulations concur thatICa,Lelevation promotes EADs and is an important determinant of long QT type 2 arrhythmia phenotype, most likely by reducing repolarization reserve and by enhancing Ca2+overload and the propensity forICa,Lreactivation.
Human Embryonic Stem Cell–Derived Cardiomyocytes and Cardiac Repair in Rodents
Authors: van Laake Linda W. , Passier Robert , Doevendans Pieter A. , Mummery Christine L.
Published: April 2008

Cell transplantation may restore heart function in disease associated with loss or dysfunction of cardiomyocytes. Recently, Laflamme et al reported an improvement in cardiac function in immunodeficient rats 4 weeks after coronary artery ligation and injection of human embryonic stem cell–derived cardiomyocytes (hESC-CMs). We have recently carried out a comparable study transplanting hESC-CMs to the hearts of mice with myocardial infarction. Our findings were similar up to the 4-week time point, with significant improvements in cardiac function. However, our follow-up was longer, and, at 3 months, the difference between mice receiving cardiomyocytes and those receiving other cells was no longer significant. Hypothesizing that the improvement observed by Laflamme et al may have been more likely to be sustained long term because the grafts in their study appeared larger, we injected 3 times as many cells. Although this resulted in a significantly increased graft size, we again observed a functional improvement at 1 month but not at 3 months. Our results show that midterm data in these kinds of experiments must be interpreted with caution and longer-term follow-up is essential to draw conclusions on the efficacy of cardiac cell transplantation. Furthermore, our findings demonstrate the unlikely success of merely generating and injecting more cells of the same type to increase functional improvement.
High Serum Levels of Endothelin-1 Predict Severe Cerebral Edema in Patients With Acute Ischemic Stroke Treated With t-PA
Authors: Moldes Octavio , Sobrino Tomás , Millán Mónica , Castellanos Mar , Pérez de la Ossa Natalia , Leira Rogelio , Serena Joaquín , Vivancos José , Dávalos Antonio , Castillo José
Published: April 2008

Background and Purpose—

Severe cerebral edema is associated with poor outcome in patients with acute stroke. Experimental studies suggest that astrocytic endothelin-1 (ET-1) has deleterious effects on water homeostasis, cerebral edema, and blood brain barrier (BBB) integrity, which contribute to more severe ischemic brain injury. In this study we analyze the association between high serum levels of ET-1 and the development of severe cerebral edema in patients treated with t-PA.

Methods—

One hundred thirty-four patients treated with t-PA according SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study) criteria were prospectively studied. Serum levels of ET-1, matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) were determined by ELISA in serum samples obtained on admission, before t-PA bolus. Severe brain edema was diagnosed if extensive swelling caused any shifting of the structures of the midline was detected on the cranial CT performed at 24 to 36 hours. Stroke severity was evaluated before t-PA administration and at 24 hours by NIHSS. Functional outcome at 3 months was evaluated by the modified Rankin Scale (mRS).

Results—

Nineteen patients (14.2%) developed severe brain edema. Median ET-1 (8.4 [6.7, 9.6] versus 1.9 [1.6, 3.2] fmol/mL,
P
<0.0001) and c-Fn (6.0 [4.1, 6.7] versus 3.2 [2.1, 4.6] mg/L,
P
<0.0001) serum levels were significantly higher in patients with severe cerebral edema. The best cut-off values for ET-1 and c-Fn serum levels for the prediction of severe brain edema were 5.5 fmol/mL (sensitivity 95% and specificity 94%) and 4.5 mg/L (sensitivity 73% and specificity 77%) respectively. ET-1 serum levels >5.5 fmol/mL before t-PA treatment were independently associated with development of severe brain edema (OR, 139.7; CI95%, 19.3 to 1012.2;
P
<0.0001), after adjustment for baseline stroke severity, early CT signs of infarction, serum levels of cFn >4.5 mg/L, and cardioembolic stroke subtype.

Conclusions—

ET-1 serum levels >5.5 fmol/mL are associated with severe brain edema in acute stroke patients treated with t-PA. These results suggest that ET-1 may be a new diagnostic marker for development of severe brain edema in patients with acute ischemic stroke treated with t-PA.
Calling 911 in Response to Stroke
Authors: Mikulík Robert , Bunt Laura , Hrdlička Daniel , Dušek Ladislav , Václavík Daniel , Krýza Jiří
Published: April 2008

Background and Purpose—

Stroke treatment is time-dependent, yet no study has systematically examined response to individual stroke symptoms in the general population. This nationwide study identifies which specific factors prompt correct response (calling 911) to stroke.

Methods—

Between November and December of 2005, a survey using a 3-stage random-sampling method including area, household, and household member sampling was conducted throughout the Czech Republic. Participants >40 years old were personally interviewed via a structured and standardized questionnaire concerning general knowledge and correct response to stroke as assessed by the Stroke Action Test (STAT). Predictors of scoring >50% on STAT were identified by multiple regression.

Results—

A total of 650 households were contacted, yielding 592 interviews (response rate 91%). Mean age was 58±12, 55% women. Sixty-nine percent thought stroke was serious condition, and 57% thought it could be treated. Also 54% correctly named ≥2 risk factors, and 46% named ≥2 warning signs. Eighteen percent of respondents scored >50% on STAT. The predictors of such a score were age (for each 10-year increment, OR 1.4, 95% CI 1.2 to 1.7), secondary school education (OR 1.7, 95% CI 1.1 to 2.6), knowing that stroke is a serious disease (OR 1.8, 95% CI 1.1 to 3.1), and knowing that stroke is treatable (OR 2.0, 95% CI 1.2 to 3.2).

Conclusions—

Knowledge about stroke in the Czech Republic was fair, yet response to warning signs was poor. Our study is the first to identify that calling 911 was influenced by knowledge that stroke is a serious and treatable disease and not by recognition of symptoms.
Filamentous Middle Cerebral Artery Occlusion Causes Ischemic Damage to the Retina in Mice
Authors: Steele Ernest C. , Guo Qingmin , Namura Shobu
Published: April 2008

Background and Purpose—

Filamentous middle cerebral artery occlusion (fMCAO) is the most frequently used focal cerebral ischemia model in rodents. The proximity of the ophthalmic artery to the middle cerebral artery suggests that fMCAO induces retinal ischemia. We therefore tested whether fMCAO induces ischemia/reperfusion damage in retina in mice.

Methods—

SV129EV mice were subjected to transient (30 or 60 minutes) fMCAO followed by reperfusion under isoflurane anesthesia. Retinal perfusion was evaluated by intravenous injection of fluorescent microspheres combined with fluorescent microscopy using flat-mounted retinas. The fluorescent density of ipsilateral retina relative to contralateral retina was determined in each animal. Retinal injury was assessed by cresyl violet staining and in situ TUNEL.

Results—

Microsphere analysis demonstrated perfusion defect in the ipsilateral retina after 60 minutes fMCAO and effective restoration after reperfusion. Thirty minutes fMCAO did not produce evident histological changes, even after 2 days of reperfusion. Sixty minutes fMCAO followed by 2 hours reperfusion resulted in extensive cell damage in the inner nuclear (>30%) and ganglion cell (>50%) layers. TUNEL demonstrated very few positive cells, suggesting that damaged cells were mainly undergoing nonapoptotic cell death.

Conclusions—

Sixty minutes fMCAO produces retinal injury in SV129EV mice. Potential visual dysfunction should be considered when a particular occlusion period is selected for studying neurological outcomes after fMCAO. Because visual disturbance is often associated with thrombotic/embolic stroke in humans, fMCAO represents an appropriate model for future studies aimed at understanding and ameliorating the changes that lead to retinal damage in these patients.
Vascular Subcortical Hyperintensities Predict Conversion to Vascular and Mixed Dementia in MCI Patients
Authors: Bombois Stéphanie , Debette Stéphanie , Bruandet Amélie , Delbeuck Xavier , Delmaire Christine , Leys Didier , Pasquier Florence
Published: April 2008

Background and Purpose—

Patients with mild cognitive impairment (MCI) have an increased risk of dementia. The identification of predictors of conversion to dementia is therefore important. The aim of our study was to test the hypothesis that subcortical hyperintensities (SH) are associated with an increased rate of conversion to dementia in MCI patients.

Methods—

This was an observational study on consecutive MCI patients attending a memory clinic. We assessed SH on a baseline MRI scan, using a semiquantitative rating scale. A multivariable Cox regression model was used to test the association of SH with conversion to dementia.

Results—

We included 170 MCI patients. The median duration of follow-up was 3.8 years. During this period, 67 patients (39.4%, 95% CI: 32.1 to 46.8%) developed dementia: Alzheimer disease (AD) in 29 patients, dementia with Lewy bodies in 19, mixed dementia in 8, vascular dementia in 7, fronto-temporal dementia in 2, and primary progressive aphasia in 2. SH were not associated with the risk to develop dementia as a whole, including AD. However, the risk to develop vascular or mixed dementia increased significantly with increasing amounts of SH at baseline (HR=1.14 [95% CI: 1.06 to 1.24]), especially periventricular hyperintensities (HR=2.71 [95% CI: 1.60 to 4.58]), independently of medial temporal lobe atrophy, age, gender, vascular risk factors, education, and cognitive functions at baseline.

Conclusion—

The risk of vascular or mixed dementia, but not of other types of dementia, was significantly increased in MCI patients with a large amount of subcortical hyperintensities at baseline.
Biomarkers of Inflammation and MRI-Defined Small Vessel Disease of the Brain
Authors: Fornage Myriam , Chiang Y. Aron , O'Meara Ellen S. , Psaty Bruce M. , Reiner Alexander P. , Siscovick David S. , Tracy Russell P. , Longstreth W.T.
Published: April 2008

Background and Purpose—

To clarify the role of inflammation in the pathogenesis of small vessel disease of the brain, we investigated the association between common variation in the C-reactive protein (CRP) and interleukin (IL)-6 genes, plasma CRP and IL6 levels, and presence of MRI-defined white matter lesions (WML) and brain infarcts (BI) in elderly participants of the Cardiovascular Health Study.

Methods—

Tag single nucleotide polymorphisms (SNPs) in the CRP and IL6 genes were selected from the SeattleSNPs database. In cross-sectional analyses, logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of plasma CRP and IL6 levels and common CRP and IL6 gene haplotypes with presence of WML or BI in Blacks (n=532) and Whites (n=2905).

Results—

Plasma IL6 and CRP levels were associated with presence of WML and BI in both races. In Whites, common haplotypes of the IL6 gene were significantly associated with WML and BI. The common haplotype tagged by the −174G/C promoter polymorphism was associated with an increased risk of WML (OR=1.14; 95% CI: [1.02; 1.28]). The common haplotype tagged by the −572G/C promoter polymorphism was associated with an increased risk of BI (OR=1.57; 95% CI: [1.15; 2.14]). Significant associations were lacking for WML or BI with IL6 gene variation in Blacks, or with CRP gene variation in either race.

Conclusions—

This study provides evidence of a genetic basis underlying the relationship between plasma biomarkers of inflammation and small vessel disease of the brain. Further studies to elucidate the specific role of IL6 in disease pathogenesis are warranted.
Effects of Thrombin on Neurogenesis After Intracerebral Hemorrhage
Authors: Yang Shuxu , Song Shuijiang , Hua Ya , Nakamura Takehiro , Keep Richard F. , Xi Guohua
Published: April 2008

Background and Purposes—

Neurogenesis in intracerebral hemorrhage (ICH) has not been investigated. Thrombin formation causes acute brain injury after ICH, but thrombin also can stimulate cell proliferation. The present study examined whether neurogenesis takes place in ICH and the role of thrombin in ICH-related neurogenesis.

Methods—

This study was divided into four parts. (1) Rats received either an ICH or a needle insertion (sham). The rats were killed for doublecortin (DCX) Western blot analysis and immunohistochemistry. (2) Rats had an ICH or a sham operation, and then received intraperitoneal injections of 5-bromo-2′-deoxyuridine (BrdU) at day-7 and day-9 later. Brains were perfused to identify BrdU-positive cells. (3) Rats had an intracaudate injection of thrombin (1 U) and brains were sampled for Western blots. (4) Rats had an ICH with or without a thrombin inhibitor, hirudin. The brains were sampled for DCX quantitation.

Results—

DCX levels in the ipsilateral basal ganglia started to increase as early as 7 days after ICH, peaked at 14 days, and then gradually decreased at 1 month. Immunohistochemistry also demonstrated that DCX immunoreactivity was increased in the ipsilateral subventricular zone and basal ganglia at 2 weeks after ICH. Some DCX-positive cells were BrdU-positive. One unit thrombin, which does not cause marked brain injury, was injected into the caudate. Thrombin increased DCX levels in the ipsilateral basal ganglia and hirudin blocked ICH-induced upregulation of DCX.

Conclusions—

Our results demonstrated that neurogenesis occurs in the brain after ICH and that thrombin may play a role in ICH-induced neurogenesis.
Tissue Microstructural Changes Are Independently Associated With Cognitive Impairment in Cerebral Amyloid Angiopathy
Authors: Viswanathan Anand , Patel Pratik , Rahman Rosanna , Nandigam R. N. Kaveer , Kinnecom Catherine , Bracoud Luc , Rosand Jonathan , Chabriat Hugues , Greenberg Steven M. , Smith Eric E.
Published: April 2008

Background and Purpose—

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive impairment and is associated with white matter hyperintensities and cerebral microbleeds. MRI diffusion tensor imaging detects microstructural tissue damage in advanced CAA even in areas that appear normal on conventional MRI. We hypothesized that higher global mean apparent diffusion coefficient (mean ADC), reflecting a higher amount of chronic tissue disruption caused by CAA, would be independently associated with CAA-related cognitive impairment.

Methods—

Preintracerebral hemorrhage cognitive impairment was systematically assessed using a standardized questionnaire (IQCODE) in 49 patients. Volume of white matter hyperintensities, number of microbleeds, and mean ADC were determined from MRIs obtained within 14.0±22.5 days of intracerebral hemorrhage cognitive impairment. White matter hyperintensities and mean ADC were measured in the hemisphere uninvolved by intracerebral hemorrhage to avoid confounding.

Results—

Preintracerebral hemorrhage cognitive impairment was identified in 10 of 49 subjects. Mean ADC was the only variable associated with preintracerebral hemorrhage cognitive impairment and was elevated in those with preintracerebral hemorrhage cognitive impairment compared with those without (12.4×10
−4
versus 11.7×10
−4
mm
2
/s;
P
=0.03). Mean ADC positively correlated with age but not white matter hyperintensities or number of microbleeds. In logistic regression controlling for age and visible cerebral atrophy, mean ADC was independently associated with preintracerebral hemorrhage cognitive impairment (OR per 1×10
−4
mm
2
/s increase=2.45, 95% CI 1.11 to 5.40,
P
=0.04).

Conclusions—

Mean ADC is independently associated with preintracerebral hemorrhage cognitive impairment in CAA. The lack of correlation with other MRI markers of CAA suggests that mean ADC may be sensitive to distinct aspects of CAA pathology and its tissue consequences. These results suggest that global MRI diffusion changes are sensitive to clinically relevant microstructural alterations and may be useful markers of CAA-related tissue damage.
Contrastive Divergence in Gaussian Diffusions
Authors: Movellan Javier R.
Published: April 2008

This letter presents an analysis of the contrastive divergence (CD) learning algorithm when applied to continuous-time linear stochastic neural networks. For this case, powerful techniques exist that allow a detailed analysis of the behavior of CD. The analysis shows that CD converges to maximum likelihood solutions only when the network structure is such that it can match the first moments of the desired distribution. Otherwise, CD can converge to solutions arbitrarily different from the log-likelihood solutions, or they can even diverge. This result suggests the need to improve our theoretical understanding of the conditions under which CD is expected to be well behaved and the conditions under which it may fail. In, addition the results point to practical ideas on how to improve the performance of CD.
A Scalable Kernel-Based Semisupervised Metric Learning Algorithm with Out-of-Sample Generalization Ability
Authors: Yeung Dit-Yan , Chang Hong , Dai Guang
Published: April 2008

In recent years, metric learning in the semisupervised setting has aroused a lot of research interest. One type of semisupervised metric learning utilizes supervisory information in the form of pairwise similarity or dissimilarity constraints. However, most methods proposed so far are either limited to linear metric learning or unable to scale well with the data set size. In this letter, we propose a nonlinear metric learning method based on the kernel approach. By applying low-rank approximation to the kernel matrix, our method can handle significantly larger data sets. Moreover, our low-rank approximation scheme can naturally lead to out-of-sample generalization. Experiments performed on both artificial and real-world data show very promising results.
Stone Roots, Digital Leaves: Czech Law against Unfair Competition in the Internet Era
Authors: Polčák Radim
Published: April 2008

The law against unfair competition is traditionally understood in countries of the Alpine legal system as extraordinary and unconventional. Unlike other legal disciplines, it does not rely on black-letter law; it is less formal and less legislatively elaborative in detail. Thus, progress and development in this area is not a matter for the legislator but for broad practically-driven doctrinal work connected to contemporary case law. When the Internet brought new opportunities in the development of business ventures, Czech law against unfair competition did not react with legislative changes but by the further development of standard interpretational patterns. In this article, we will briefly describe the grounds as well as recent related developments in the Czech law against unfair competition connected to unfair business practices on the Internet.
Intellectual Property in an Innovation-based Economy
Authors: Pisuke Heiki , Kelli Aleksei
Published: April 2008

The process of transformation into an innovation-based economy has had a considerable impact on the intellectual property (IP) system. IP has become an integral part of innovative processes. These developments have led to changes in IP concepts. The authors argue that the notion of IP must include both legal (IP as rights) and economic (IP as an asset) aspects. The balance between different kinds of IP (copyright, related rights, industrial property) within innovation processes should be reviewed in order to acknowledge the rightful place of copyright as the core of IP and IP culture. Nevertheless, the major tools for enhancing innovation are still based on industrial property. The role of IP in different kinds of policy documents should be increased. In order to fully exploit the potential of IP, it is necessary to enhance the development of supportive infrastructure for the utilization and commercialization of IP (intellectual infrastructure). Such infrastructure should support the functioning of IP systems, identifying new knowledge and transfering knowledge from entrepreneurial universities to industry. Raising public awareness about practical aspects of IP and fostering IP competencies are of paramount importance. Teaching IP at universities and adopting university IP policies form an important part of this process. According to the vision of the authors, a basic course on IP should be taught at every university to all students. Specialized IP courses should be part of the curricula at the faculties of law, economics, engineering, biology, philosophy, etc. The authors outline the Estonian experience with regard to these issues.
Horizontal and Vertical Structure of Easterly Waves in the Pacific ITCZ
Authors: Serra Yolande L. , Kiladis George N. , Cronin Meghan F.
Published: April 2008

Outgoing longwave radiation (OLR) and low-level wind fields in the Atlantic and Pacific intertropical convergence zone (ITCZ) are dominated by variability on synoptic time scales primarily associated with easterly waves during boreal summer and fall. This study uses spectral filtering of observed OLR data to capture the convective variability coupled to Pacific easterly waves. Filtered OLR is then used as an independent variable to isolate easterly wave structure in wind, temperature, and humidity fields from open-ocean buoys, radiosondes, and gridded reanalysis products. The analysis shows that while some Pacific easterly waves originate in the Atlantic, most of the waves appear to form and strengthen within the Pacific. Pacific easterly waves have wavelengths of 4200–5900 km, westward phase speeds of 11.3–13.6 m s−1, and maximum meridional wind anomalies at about 600 hPa. A warm, moist boundary layer is observed ahead of the waves, with moisture lofted quickly through the troposphere by deep convection, followed by a cold, dry signal behind the wave. The waves are accompanied by substantial cloud forcing and surface latent heat flux fluctuations in buoy observations. In the central Pacific the horizontal structure of the waves appears as meridionally oriented inverted troughs, while in the east Pacific the waves are oriented southwest–northeast. Both are tilted slightly eastward with height. Although these tilts are consistent with adiabatic barotropic and baroclinic conversions to eddy energy, energetics calculations imply that Pacific easterly waves are driven primarily by convective heating. This differs from African easterly waves, where the barotropic and baroclinic conversions dominate.