bluuebunny/crossref_metadata_2025_split huggingface dataset:
The formation of trajectories during goal‐oriented locomotion in humans. II. A maximum smoothness model
Authors: Pham Quang‐Cuong , Hicheur Halim , Arechavaleta Gustavo , Laumond Jean‐Paul , Berthoz Alain 
Published: October 2007

AbstractDespite the theoretically infinite number of possible trajectories a human may take to reach a distant doorway, we observed that locomotor trajectories corresponding to this task were actually stereotyped, both at the geometric and the kinematic levels. In this paper, we propose a computational model for the formation of human locomotor trajectories. Our model is adapted from smoothness maximization models that have been studied in the context of hand trajectory generation. The trajectories predicted by our model are very similar to the experimentally recorded ones. We discuss the theoretical implications of this result in the context of movement planning and control in humans. In particular, this result supports the hypothesis that common principles, such as smoothness maximization, may govern the generation of very different types of movements (in this case, hand movements and whole‐body movements).
A spiking network model for passage‐of‐time representation in the cerebellum
Authors: Yamazaki Tadashi , Tanaka Shigeru 
Published: October 2007

AbstractIn Pavlovian delay eyeblink conditioning, the cerebellum represents the passage‐of‐time (POT) between onsets of conditioned and unconditioned stimuli (CS and US, respectively). To study possible computational mechanisms of the POT representation we built a large‐scale spiking network model of the cerebellum. Consistent with our previous rate‐coding model, we found two conditions necessary for the present model to represent the POT with a dynamic population of active granule cells: (i) long temporal integration of input signals; and (ii) random recurrent connections between granule and Golgi cells. When these conditions were satisfied, a nonrecurrent sequence of active granule cell populations was generated in response to a CS and, conversely, the POT from the CS onset was able to be read out from the sequence. Specifically, simulated N‐methyl‐D‐aspartate (NMDA) channels with a long decay time constant at granule and Golgi cells were responsible for the long temporal integration. Thus, blocking the NMDA channels or ablating Golgi cells impaired the POT representation. Simulated glomerulus structure made POT representation robust against noise in mossy fibre inputs. Long‐term potentiation induced at mossy fibre synapses on granule cells also served to enhance the robustness. We reproduced some experimental results of Pavlovian delay eyeblink conditioning using the present model. These results suggest that the recurrent network in the granular layer and NMDA channels in granule and Golgi cells play an essential role in the timing mechanisms in the cerebellum, whereas the glomerulus serves to realize a robust representation of time.
Inactivation of the gene for the nuclear receptor tailless in the brain preserving its function in the eye
Authors: Belz Thorsten , Liu Hai‐Kun , Bock Dagmar , Takacs Andrea , Vogt Miriam , Wintermantel Tim , Brandwein Christiane , Gass Peter , Greiner Erich , Schütz Günther 
Published: October 2007

AbstractDuring embryogenesis, tailless, an orphan member of the nuclear receptor family, is expressed in the germinal zones of the brain and the developing retina, and is involved in regulating the cell cycle of progenitor cells. Consequently, a deletion of the tailless gene leads to decreased cell number with associated anatomical defects in the limbic system, the cortex and the eye. These structural abnormalities are associated with blindness, increased aggressiveness, poor performance in learning paradigms and reduced anxiousness. In order to assess the contribution of blindness to the behavioural changes, we established tailless mutant mice with intact visual abilities. We generated a mouse line in which the second exon of the tailless gene is flanked by loxP sites and crossed these animals with a transgenic line expressing the Cre recombinase in the neurogenic area of the developing brain, but not in the eye. The resulting animals have anatomically indistinguishable brains compared with tailless germline mutants, but are not blind. They are less anxious and much more aggressive than controls, like tailless germline mutants. In contrast to germline mutants, the conditional mutants are not impaired in fear conditioning. Furthermore, they show good performance in the Morris water‐maze despite severely reduced hippocampal structures. Thus, the pathological aggressiveness and reduced anxiety found in tailless germline mutants are due to malformations caused by inactivation of the tailless gene in the brain, but the poor performance of tailless null mice in learning and memory paradigms is dependent on the associated blindness.
Shifting and scaling adaptation to dynamic stimuli in somatosensory cortex
Authors: Garcia‐Lazaro J. A. , Ho S. S. M. , Nair A. , Schnupp J. W. H. 
Published: October 2007

AbstractRecent reports have shown that responses of midbrain neurons in the guinea pig rapidly shift the dynamic range of their responses to track changes in the statistics of ongoing sound‐level distributions. This results in an increased coding accuracy for the most commonly occurring stimulus intensities. To investigate whether this type of adaptation might also be found in other sensory modalities, we characterized the intensity–response functions of neurons in rat primary somatosensory cortex (S1) to continuous sinusoidal vibration of the whiskers with amplitudes that were changed every 40 ms. Vibration amplitudes were selected randomly such that there was an 80% chance for the amplitude to be drawn from a relatively narrow ‘high‐probability region’ (HPR). Stimulus mean and variance were then manipulated by shifting or widening the HPR. We found that rat S1 neurons adapt to shifts of the HPR mainly by shifting their thresholds, and to changes in HPR width by changing the slope of their rate‐level curves. Using realistic single‐neuron models, we go on to show that after‐hyperpolarizing currents, such as those carried by KCa2+ channels, may be responsible for the threshold shifts, but not the slope changes.
Postoperative methemoglobinemia following infiltrative lidocaine administration for combined anesthesia in pediatric craniofacial surgery
Authors: NEUHAEUSER CHRISTOPH , WEIGAND NIKOLA , SCHAAF HEIDRUM , MANN VALESCO , CHRISTOPHIS PETROS , HOWALDT HANS PETER , HECKMANN MATTHIAS 
Published: October 2007

SummaryBackground: Infiltrative anesthesia of the scalp with lidocaine was used in an attempt to reduce blood loss and anesthetic requirements during pediatric craniofacial surgery. Lidocaine, however, has the potential to cause methemoglobinemia. In this retrospective cohort‐study we analyzed the incidence and effects of postoperative methemoglobinemia following subcutaneous lidocaine administration.Methods: During 1999–2006, 50 infants (age: 3–31 months) undergoing elective craniofacial surgery were analyzed. All infants received general anesthesia and routine monitoring, including invasive arterial blood pressure measurement. Prior to incision, the scalp was infiltrated with 6–15 ml lidocaine 1% (with epinephrine 1 : 200.000). Blood loss and blood transfusions were recorded. Methemoglobin (Met‐Hb) levels were determined postoperatively using co‐oximetry.Results: Twenty percent of the operated infants showed elevated Met‐Hb levels (median of maximal levels: 6%; range: 2.2–18%) at admission on the PICU. In 80% of these methemoglobinemia resolved spontaneously within 12 h, only two children received methylene blue because of visible cyanosis. The intra‐ and postoperative course was otherwise uneventful in all the children despite significant total blood loss (median of blood loss as percentage from total estimated blood volume: 43%; range: 11–110%). Lidocaine was the only substance identified to have the potential to cause methemoglobinemia. However, the average administered dose of lidocaine was not significantly different between patients with or without methemoglobinemia (13 ± 3.1 vs 12 ± 3.5 mg·kg−1;P = 0.37).Conclusions: Even though we did not measure lidocaine plasma levels, lidocaine was the most likely cause of postoperative methemoglobinemia. Despite a high incidence, methemoglobinemia occurred sporadically and was without dangerous consequences.
The use of aprotinin in children undergoing operative repair of isolated atrial septal defects
Authors: CHIRAVURI S. DEVI , VOEPEL‐LEWIS TERRI , DEVANEY ERIC J. , MALVIYA SHOBHA 
Published: October 2007

SummaryBackground:  The purpose of this retrospective study was to examine the benefits, risks and costs associated with aprotinin use in children who underwent repair of an atrial septal defect (ASD). The primary aim was to determine whether the transfusion rate is lower in children who received aprotinin compared with those who did not during ASD repair. The use of aprotinin has been shown to reduce transfusion requirements for children undergoing primary or secondary repair of congenital cardiac anomalies. However, past studies have not reported the benefits of this agent during low complexity procedures such as ASD repair.Methods:  All children who underwent ASD repair over 6 years (3 years pre‐ and postroutine use of aprotinin for all CPB cases in the institution) were identified, and their medical records reviewed. Children with multiple congenital cardiac lesions were excluded. The following data were recorded: demographics and baseline laboratory findings, intraoperative use of aprotinin, cardiopulmonary bypass information including details of ultrafiltration, all intraoperative and postoperative transfusions, postoperative bleeding and relevant laboratory findings.Results:  One hundred and fifteen children were included, 66 of whom received aprotinin. Transfusion rates were not different between children who received aprotinin [n = 8 (12%)] and those who did not [n = 3 (6%)]. Furthermore, changes in hematocrit were not different between groups. These findings were similar when children ≤15 kg were compared with those >15 kg.Conclusions:  This study suggests that aprotinin use offers no benefit for children undergoing isolated repair of an ASD.
Maternal heart rate variability just before surgery significantly correlated with emergence behavior of children undergoing general anesthesia
Authors: ARAI YOUNG‐CHANG P. , UEDA WASA , ITO HIROSHI , WAKAO YOSHIKO , MATSURA MASAYO , KOMATSU TORU 
Published: October 2007

SummaryBackground:  Emergence agitation in pediatric anesthesia is associated with preanesthesia child anxiety, which is strongly influenced by maternal mental conditions. Mental stress affects the autonomic nervous system, thereby influencing heart rate variability (HRV). The present study tested the correlations between preanesthesia maternal HRV and perioperative child behavior.Methods:  A total of 27 pairs of mothers and children were analyzed in the present study. Maternal HRV was recorded from the night before the child’s surgery to arrival to the operation room and thereafter recorded data were analyzed. The children underwent minor plastic surgery under general anesthesia, and induction and emergence behavior were assessed.Results:  Quality of mask induction did not correlate with the ratio of low‐frequency (LF) components to high‐frequency (HF) components (LF/HF ratio) of preanesthesia maternal HRV either obtained during 21:00–06:00 (stage I) or 06:00–08:00 (stage II). Scores of the child’s emergence behavior did not correlate with the LF/HF ratio of maternal HRV of stage I; however, the LF/HF ratio of maternal HRV of stage II significantly correlated with emergence behavior.Conclusions:  Two‐hour maternal HRV just before surgery significantly correlated with emergence behavior of children undergoing general anesthesia.
Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment‐naïve elderly patients with type 2 diabetes
Authors: Schwarz S. L. , Gerich J. E. , Marcellari A. , Jean‐Louis L. , Purkayastha D. , Baron M. A. 
Published: October 2007

Aim:  The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM).Methods:  Study 1 was a 12‐week, multicentre, randomized, double blind and placebo‐controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug‐naïve patients with T2DM aged ≥65 years. Study 2 was a 104‐week, multicentre, randomized, double blind and active‐controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment‐naïve patients with T2DM aged ≥65 years. HbA1c, fasting and postprandial glucose levels, and safety assessments were made.Results:  In Study 1, nateglinide significantly reduced HbA1c from baseline (7.6 ± 0.1% to 6.9 ± 0.1%; Δ = −0.7 ± 0.1%, p < 0.001) and compared with placebo (between‐group difference = −0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA1c from baseline (7.8 ± 0.2% to 6.6 ± 0.1%; Δ = −1.2 ± 0.2%, p < 0.001), as did glyburide/metformin (7.7 ± 0.1% to 6.5 ± 0.1%; Δ = −1.2 ± 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin‐treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA1c (<7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin‐treated patients (Study 2).Conclusion:  Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.
Addition of biphasic insulin aspart 30 to optimized metformin and pioglitazone treatment of type 2 diabetes mellitus: The ACTION Study (Achieving Control Through Insulin plus Oral ageNts)
Authors: Raskin P. , Matfin G. , Schwartz S. L. , Chaykin L. , Chu P.‐L. , Braceras R. , Wynne A. 
Published: October 2007

Aim:  Efficacy and safety of biphasic insulin aspart (BIAsp 30, 30% short‐acting and 70% intermediate‐acting insulin aspart) added to an optimized treatment of metformin and pioglitazone (met/pio) were compared with treatment with optimized met/pio in type 2 diabetes patients.Methods:  This randomized, 34‐week, parallel‐group study enrolled insulin‐naive, type 2 diabetes patients (HbA1c 7.5–12.0%) previously using two oral antidiabetic (OAD) agents. During an 8‐week run‐in period, treatment was changed to met/pio and doses were adjusted up to 2500 mg/day and 30 or 45 mg/day respectively. Subjects either continued met/pio alone or added BIAsp 30 initiated at 6 units twice daily and titrated to target plasma glucose (PG) (4.4–6.1 mmol/l).Results:  At end‐of‐study, subjects treated with BIAsp 30+met/pio (n = 93) had a mean (±s.d.) HbA1c reduction significantly greater than treatment with met/pio (n = 88) (1.5% ± 1.1 vs. 0.2% ± 0.9, p < 0.0001 between groups). Subjects treated with BIAsp 30+met/pio were more likely to reach The American Association of Clinical Endocrinologists and European Association for the Study of Diabetes/American Diabetes Association HbA1c targets of ≤6.5 and <7.0%, respectively, than with met/pio only (HbA1c≤6.5%: 59 vs. 12%; HbA1c <7.0%: 76 vs. 24%). At end‐of‐study, self‐monitored glucose profile values at all eight daily time points were significantly less for the BIAsp 30+met/pio group compared with the met/pio group, and minor hypoglycaemia (defined as PG < 3.1 mmol/l) was more frequent (8.3 vs. 0.1 events/year, p < 0.001). Both groups gained weight during treatment (BIAsp 30+met/pio, 4.6 ± 4.3 kg; met/pio, 0.8 ± 3.2 kg; p < 0.001).Conclusion:  Addition of insulin in type 2 patients treated with met/pio is an effective way to achieve glycaemic targets. Treatment with BIAsp 30+met/pio achieved significantly greater reduction in HbA1c, as compared with met/pio alone. In patients with type 2 diabetes poorly controlled by 2 OADs, more achieved glycaemic targets using BIAsp 30+met/pio than using met/pio alone.
Effect of atorvastatin on endothelial function and inflammation in long‐duration type 1 diabetic patients without coronary heart disease and arterial hypertension
Authors: Konduracka E. , Galicka‐Latala D. , Cieslik G. , Rostoff P. , Fedak D. , Sieradzki J. , Naskalski J. , Piwowarska W. 
Published: October 2007

Aim:  We evaluated the ability of atorvastatin, an HMG‐CoA reductase inhibitor, to affect endothelial function and inflammation in long‐duration (>10 years) type 1 diabetes mellitus (T1DM) patients without coronary heart disease (CHD) and arterial hypertension (AH).Methods and Results:  We randomized 204 Caucasians with long‐duration T1DM into either the atorvastatin 40 mg/day plus hypolipaemic diet group (n = 154) or the placebo plus hypolipaemic diet group (n = 50) for 6 months. Endothelium‐dependent flow‐mediated (FMD) and endothelium‐independent flow‐mediated vasodilatation, serum levels of plasminogen activator inhibitor‐1 (PAI‐1), von Willebrand factor (vWF) and high sensitivity C‐reactive protein (hs‐CRP) were estimated before and after treatment. After 6 months of therapy, FMD was increased by 44% in the atorvastatin plus diet group compared with the placebo plus diet group. Treatment with atorvastatin led to a significant reduction in levels of PAI‐1 and hs‐CRP; however, the elevation of vWF level was observed. In the placebo plus diet group, we observed a significant reduction in levels of hs‐CRP but not of vWF and PAI‐1.Conclusions:  Atorvastatin improves endothelial function and reduces some proinflammatory and prothrombotic markers of atherosclerosis in T1DM patients without CHD and AH. The surprising effect of atorvastatin on serum vWF levels in T1DM requires further study.
Weight changes in type 2 diabetes and the impact of gender
Authors: Tuthill A. , McKenna M. J. , O’Shea D. , McKenna T. J. 
Published: October 2007

Aims:  Many studies suggest that weight gain occurs during treatment of type 2 diabetes, irrespective of the treatment type. The aim of this study was to address the questions (i) whether weight gain is inevitable in patients treated for type 2 diabetes, and (ii) whether treatment escalation is prompted by a rise in glycaemic control [haemoglobin A1c (HbA1c)] or weight gain.Methods:  A diabetes database was used to identify all patients with type 2 diabetes attending our clinic between 1 January 1990 and 31 December 2000. To facilitate further analysis, independent anonymized database resources were established. Data collected included height, weight, gender, HbA1c, age and diabetes treatment at each visit.Results:  One thousand and eighty‐four patients were included; after 6 months of treatment, patients’ average weight had reduced by 1.0 kg (s.d. 4.6) (p < 0.001). Sixty per cent of the patients had either a decrease or no change in weight, while 40% demonstrated a weight gain. Women demonstrated more weight loss than men. After a mean follow‐up of 50 months (s.d. 25.7), 439 patients (40%) who received treatment with diet alone, diet followed by metformin or metformin alone demonstrated a maintained weight reduction in addition to improved glycaemic control. A rise in HbA1c rather than weight gain prompted treatment change.Conclusions:  This study provides evidence that weight gain is not a necessary consequence of the treatment of type 2 diabetes. Women were more successful than men in losing weight, and diet, with or without the addition of metformin, was the treatment type most usually associated with weight loss.
Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes
Authors: Brooks B. A. , Franjic B. , Ban C. R. , Swaraj K. , Yue D. K. , Celermajer D. S. , Twigg S. M. 
Published: October 2007

Aim:  Diabetic cardiomyopathy is an increasingly recognized entity. The pathogenic factors that may contribute to its development, especially the earliest changes of diastolic dysfunction (DD), have not been clearly defined. Microvessel dysfunction and upregulation of profibrotic growth factors have been described as possible causes. The aim of this study was therefore to determine whether microvascular dysfunction and/or upregulation of the profibrotic connective tissue growth factor (CTGF) are associated with subclinical DD in subjects with type 2 diabetes.Methods:  Forty subjects with type 2 diabetes and 20 age‐matched non‐diabetic controls, all of whom had no clinical evidence of ischaemic heart disease, cardiac failure or echo evidence of systolic ventricular dysfunction, were recruited. Microvascular function was measured by laser Doppler velocimetry, with examination of endothelium‐dependent increase in blood flow following iontophoresis of acetylcholine (ACh) and endothelium‐independent increase in blood flow in response to the nitric oxide donor sodium nitroprusside (SNP). CTGF levels were determined by Western immunoblotting.Results:  DD determined on the basis of traditional echocardiographic criteria was similar in diabetic subjects compared with controls (28 vs. 20%, p = 0.5). Using left ventricular myocardial tissue Doppler‐based indices for DD, the E/E′ and the E′/A′ ratios (where E is the flow related to early ventricular filling and E′ and A′ are early and late diastolic velocities, respectively) in diabetic subjects revealed evidence of more DD than controls (p = 0.046 and p = 0.007 respectively) . Comparing controls with no DD by conventional echocardiographic criteria (Group I), diabetes and no DD (Group II) and diabetes with DD (Group III), there was a significant trend in reduction of both endothelium‐dependent (ACh fold change; p = 0.04) and endothelium‐independent (SNP fold change; p = 0.0004) blood flow across the groups. The ACh and SNP responses, however, were not correlated significantly with quartiles of the E/E′ ratio or the E′/A′ ratio. CTGF plasma levels did not differ across the groups and CTGF did not correlate with parameters of microvascular function.Conclusions:  This study indicates that while there is a significant association between DD and measures of microvascular function, the relationship between endothelial dysfunction, CTGF and subtle measures of DD is not strong. Other factors are therefore likely to play an important role in the early pathogenesis of subclinical cardiac DD in type 2 diabetes.
Co‐administration of SR141716 with peptide YY3–36 or oxyntomodulin has additive effects on food intake in mice
Authors: White N. E. , Dhillo W. S. , Liu Y.‐L. , Small C. J. , Kennett G. A. , Gardiner J. V. , Ghatei M. A. , Bloom S. R. 
Published: October 2007

Background:  SR141716 has been shown to significantly inhibit food intake and reduce body weight by antagonizing CB1 receptors. The gut hormones peptide YY3–36 (PYY3–36) and oxyntomodulin (OXM) inhibit food intake through Y2 and Glucagon‐Like‐Peptide (GLP)‐1 receptors respectively.Objective:  To determine the effects of co‐administration of SR141716 with either PYY3–36 or OXM in mice on food intake.Methods:  Mice (n = 14 per group) were fasted for 16 h prior to study days and given two intraperitoneal injections: study 1, vehicle–saline, SR141716–saline, vehicle–PYY3–36 or SR141716–PYY3–36; study 2: vehicle–saline, SR141716–saline, vehicle–OXM or SR141716–OXM.Food was returned and measured following injections.Results:  Co‐administration of SR141716–PYY3–36 or SR141716–OXM showed greater inhibition in food intake when compared with administration of SR141716, PYY3–36 or OXM alone.Conclusion:  Our data show that SR141716 in combination with PYY3–36 or OXM reduces food intake additively in mice.