bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cinnamtannin B‐1 on cholecystokinin‐8‐evoked responses in mouse pancreatic acinar cells
Authors: Rivera‐Barreno Ramon , Castillo‐Vaquero Angel del , Salido Gines M , Gonzalez Antonio
Published: July 2010

1. Cinnamtannin B‐1 is a naturally occurring A‐type proanthocyanidin that belongs to a class of polyphenols widely distributed throughout the plant kingdom and exhibiting anti‐oxidant properties.

2. In the present study, we examined the effects of cinnamtannin B‐1 on cholecystokinin octapeptide (CCK‐8)‐evoked Ca2+mobilization, reactive oxygen species (ROS) production and amylase secretion in the exocrine pancreas.

3. Stimulation of cells with 1 nmol/L CCK‐8 led to a transient increase in the cytosolic free calcium concentration ([Ca2+]c), followed by a decrease towards a value close to the prestimulation level. In the presence of 10 μmol/L cinnamtannin B‐1, stimulation of cells with CCK‐8 resulted in a smaller [Ca2+]cpeak response, a faster rate of decay of [Ca2+]cand lower values for the steady state of [Ca2+]c, compared with the effect of CCK‐8 alone. Cinnamtannin B‐1 decreased Ca2+influx after depletion of intracellular stores by either CCK‐8 or thapsigargin (1 μmol/L). Conversely, CCK‐8 increased the fluorescence of 5‐(and‐6)‐chloromethyl‐2′,7′‐dichlorodihydrofluorescein diacetate acetyl ester (CM‐H2DCFDA), reflecting an increase in oxidation. Cinnamtannin B‐1 reduced CCK‐8‐induced oxidation of CM‐H2DCFDA. Cholecystokinin‐8 had a biphasic effect on amylase secretion, producing maximum at a concentration of 0.1 nmol/L and reducing secretion at higher concentrations. Pre‐incubation of cells with 10 μmol/L cinnamtannin B‐1 significantly attenuated the inhibition of enzyme secretion in response to high concentrations of CCK‐8 (i.e. >10−10 mol/L). Finally, the anti‐oxidant protected acinar cells against CCK‐8‐induced cell death.

4. The beneficial effects of cinnamtannin B‐1 appear to be mediated by a reduction in intracellular Ca2+overload, ROS production and intracellular accumulation of digestive enzymes, which is a common pathological precursor that mediates pancreatitis.
Dobutamine‐induced mechanical alternans is a marker of poor prognosis in idiopathic dilated cardiomyopathy
Authors: Hirashiki Akihiro , Izawa Hideo , Cheng Xian Wu , Unno Kazumasa , Ohshima Satoru , Murohara Toyoaki
Published: July 2010

1. To date, few prognostic indicators for ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) have been identified. The purpose of the present study was to investigate the relationship between the occurrence of dobutamine‐induced mechanical alternans (MA) and prognosis in ambulatory patients with IDCM.

2. Left ventricular pressure was measured during right atrial pacing and after intravenous infusion of dobutamine at incremental doses in 90 ambulatory patients with IDCM in sinus rhythm. Endomyocardial biopsy specimens were also obtained for quantitative analysis of gene expression. The patients were followed up for a mean of 2.5 years.

3. Patients were classified into three groups: (i) 60 patients who exhibited neither pacing‐ nor dobutamine‐induced MA (Group N); (ii) 20 patients who manifested only pacing‐induced MA (Group P); and (iii) 10 patients who developed both pacing‐ and dobutamine‐induced MA (Group D). The sarcoplasmic/endoplasmic reticulum calcium ATPase 2a : phospholamban mRNA ratio was significantly higher in Group D patients than in patients in Groups N or P. Multivariate analysis revealed that dobutamine‐induced MA (odds ratio 4.05; 95% confidence interval 1.35–12.2) was a significant independent predictor of cardiac events. Cardiac event‐free survival in Group D was significantly lower than in Groups N or P, as determined by Kaplan–Meier analysis (P = 0.002).

4. The occurrence of dobutamine‐induced MA is a potentially useful clinical predictor of poor prognosis in ambulatory patients with IDCM in sinus rhythm.
Spatially and temporally regulated expression of specific heparan sulfate epitopes in the developing mouse olfactory system
Authors: Takatoh Jun , Hanaoka Kazunori
Published: July 2010

Heparan sulfate (HS) comprises a structurally diverse group of glycosaminoglycans present ubiquitously on cell surfaces and in the extracellular matrix. The spatially and temporally regulated expression of specific HS structures is essential for various developmental processes in the nervous system but their distributions in the mouse olfactory system have not been explored. Here, we examined the spatiotemporal distribution of particular HS species in the developing mouse olfactory system using three structure‐specific monoclonal antibodies (HepSS‐1, JM403 and NAH46). The major findings were as follows. (i) During olfactory bulb morphogenesis, the HepSS‐1 epitope was strongly expressed in anterior telencephalic cells and coexpressed with fibroblast growth factor receptor 1. (ii) In early postnatal glomeruli, the JM403 epitope was expressed at different levels among individual glomeruli. The expression pattern and levels of the JM403 epitope were both associated with those of ephrin‐A3. (iii) In the vomeronasal system, the JM403 epitope was expressed in all vomeronasal axons but became increasingly restricted to vomeronasal axons terminating in the anterior region of the accessory olfactory bulb by 3 weeks of age. Our results demonstrate that each HS epitope exhibits a unique expression pattern during the development of the mouse olfactory system. Thus, each HS epitope is closely associated with particular developmental processes of the olfactory system and might have a particular role in developmental events.
Hepatitis B virus genotype B results in better immediate, late and sustained responses to peginterferon‐alfa in hepatitis‐B‐e‐antigen‐positive patients
Authors: Chen Chien‐Hung , Lee Chuan‐Mo , Hung Chao‐Hung , Wang Jing‐Houng , Hu Tsung‐Hui , Changchien Chi‐Sin , Lu Sheng‐Nan
Published: July 2010

Background and Aims:  This study investigated outcome predictors in hepatitis‐B‐e‐antigen (HBeAg)‐positive chronic hepatitis B patients treated with peginterferon alfa‐2a.

Methods:  A total of 88 HBeAg‐positive patients receiving peginterferon alfa‐2a for 6 months and followed up for at least 24 weeks were prospectively analyzed. Precore and core promoter genes of hepatitis B virus (HBV) were sequenced from the serial serum samples of 88 patients.

Results:  After 24 weeks of follow up, 38.6% and 28.4% of patients achieved HBeAg clearance and combined response, respectively. Multivariate analysis disclosed that pretreatment HBeAg sample to cut‐off (S/Co) ratio ≤ 200, alanine aminotransferase > 200 IU/mL, HBV genotype B and T1846 were independent factors for HBeAg clearance, and HBeAg S/Co ratio ≤ 200 and HBV genotype B were major determinants for combined response. HBeAg S/Co ratio ≤ 10 at week 12 of therapy was the useful factor for treatment response and had a greater power (P = 0.012) to predict HBeAg clearance than HBV DNA. Patients with HBeAg clearance had a higher frequency of A1896 mutation at baseline and during therapy than those without HBeAg clearance, and the frequency of A1896 decreased during treatment. During follow up, delayed HBeAg seroconversion and reactivation of HBV after HBeAg clearance were observed in eight non‐responders and 20 patients with HBeAg clearance, respectively. HBV genotype B was a significant factor to predict both responses.

Conclusions:  Pretreatment HBeAg S/Co ratio ≤ 200 and HBV genotype B were major determinants for treatment response to peginterferon. Genotype‐B‐infected patients had higher probability of delayed HBeAg clearance and sustained response. Rapid decrease of HBeAg titer was useful on treatment predictor.
Neurodevelopmental and audiological outcome of healthy term newborns with moderately severe non‐haemolytic hyperbilirubinemia
Authors: Heimler Ruth , Sasidharan Ponthenkandath
Published: July 2010

Objective:  Our objective was to examine the outcome of term infants who developed moderate non‐haemolytic jaundice as information regarding the neurodevelopmental outcome of term infants with moderately severe non‐haemolytic hyperbilirubinemia remains controversial.

Study design:  Thirty‐nine term infants rehospitalised with non‐haemolytic hyperbilirubinemia (serum bilirubin levels: 20–30 mg/dL) during the first 2 weeks of life (study group), were assessed and compared to 36 children born at term who did not develop neonatal jaundice (control group). Assessment consisted of the Bailey 2 test, speech evaluation, behavioural hearing test and a neurological examination.

Results:  The subjects were assessed at a mean age of 3 years. There was no difference between the groups with regard to background data, except for the mean gestational age (38 + 1.3 weeks (study group) vs. 39.5 + 1.4 weeks (control group), P= 0.01). There were no significant differences between the groups in outcome parameters initially, and after correcting for possible confounding factors. None of the children in either of the groups had a neurosensory hearing deficit or any significant neurological deficiency. There was no correlation of outcome parameters with the admission serum Bilirubin levels or with the duration of hyperbilirubinemia.

Conclusion:  No untoward outcome was found in term healthy infants with moderately severe non‐haemolytic hyperbilirubinemia. Moreover, we did not find a correlation of outcome with serum bilirubin levels or with the duration of the hyperbilirubinemia in the study group.
Recent consumption of a large meal does not affect measurements of lung function
Authors: CHU Elise , BURTON Debbie , MCARDLE Nigel , GAIN Kevin
Published: July 2010

Background and objective:  It is currently recommended that patients avoid large meals prior to their lung function tests. The aim of this study is to determine whether this recommendation is necessary in clinical practice.

Methods:  A randomized controlled cross‐over trial was conducted. Subjects performed lung function tests (spirometry, measurement of lung volumes and gas transfer) prior to, directly following and 2 h after consuming a large breakfast. On the control arm, subjects performed the same lung function tests while fasting for the duration of the morning. The study subjects comprised 12 healthy subjects, 10 COPD patients and 10 patients with interstitial lung disease.

Results:  There were no significant differences between measurements on the meal and control days for FEV1, FVC, TLC or DLCO. There were no significant changes with time in any of these parameters over the course of either the meal or control morning.

Conclusions:  Common measures of lung function are not affected by the prior consumption of a large meal and it is unnecessary to advise patients to avoid a large meal prior to lung function assessment.
Urokinase‐type plasminogen activator system and human cationic antimicrobial protein 18 in serum and induced sputum of patients with chronic obstructive pulmonary disease
Authors: JIANG Yuanyuan , XIAO Wei , ZHANG Yi , XING Ying
Published: July 2010

Background and objective:  There is increasing evidence that the innate immune system plays an important role in the pathogenesis of COPD. The objective of this study was to quantify several innate immune biomarkers in serum and induced sputum of COPD patients, and healthy non‐smokers and smokers.

Methods:  Serum and induced sputum levels of urokinase‐type plasminogen activator (uPA), urokinase‐type plasminogen activator receptor (uPAR), urokinase‐type plasminogen activator inhibitor (PAI‐1) and human cationic antimicrobial protein 18 (CAP18) were measured by ELISA, in 13 patients with stage I or stage II COPD (COPD I + II), 15 patients with stage III or stage IV COPD (COPD III + IV), 18 healthy non‐smokers and 14 healthy smokers. In addition, membrane‐bound uPAR in peripheral blood and induced sputum was assessed by flow cytometry.

Results:  Levels of uPAR, PAI‐1 and CAP18 were elevated in induced sputum of COPD I + II and COPD III + IV patients, compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). uPAR, PAI‐1 and CAP18 levels were significantly higher in COPD III + IV patients compared with COPD I + II patients (P < 0.05). The expression of uPAR on induced sputum neutrophils and macrophages was significantly higher in COPD patients compared with healthy non‐smokers (P < 0.05) and healthy smokers (P < 0.05). Sputum uPAR and CAP18 levels showed significant inverse correlations with FEV1% and 6MWD, and significant positive correlations with St. George's Respiratory Questionnaire scores.

Conclusions:  In COPD patients, increased induced sputum levels of uPAR, PAI‐1 and CAP18 were associated with airflow limitation, health status and exercise tolerance, suggesting that these biomarkers may be implicated in the pathogenesis of COPD.
Sensory and cortical activation of distinct glial cell subtypes in the somatosensory thalamus of young rats
Authors: Parri H. Rheinallt , Gould Timothy M. , Crunelli Vincenzo
Published: July 2010

The rodent ventrobasal (VB) thalamus receives sensory inputs from the whiskers and projects to the cortex, from which it receives reciprocal excitatory afferents. Much is known about the properties and functional roles of these glutamatergic inputs to thalamocortical neurons in the VB, but no data are available on how these afferents can affect thalamic glial cells. In this study, we used combined electrophysiological recordings and intracellular calcium ([Ca2+]i) imaging to investigate glial cell responses to synaptic afferent stimulation. VB thalamus glial cells can be divided into two groups based on their [Ca2+]i and electrophysiological responses to sensory and corticothalamic stimulation. One group consists of astrocytes, which stain positively for S100B and preferentially load with SR101, have linear current–voltage relations and low input resistance, show no voltage‐dependent [Ca2+]i responses, but express mGluR5‐dependent [Ca2+]i transients following stimulation of the sensory and/or corticothalamic excitatory afferent pathways. Cells of the other glial group, by contrast, stain positively for NG2, and are characterized by high input resistance, the presence of voltage‐dependent [Ca2+]i elevations and voltage‐gated inward currents. There were no synaptically induced [Ca2+]i elevations in these cells under control conditions. These results show that thalamic glial cell responses to synaptic input exhibit different properties to those of thalamocortical neurons. As VB astrocytes can respond to synaptic stimulation and signal to neighbouring neurons, this glial cell organization may have functional implications for the processing of somatosensory information and modulation of behavioural state‐dependent thalamocortical network activities.
Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes
Authors: Diniz Daniel G. , Foro César A. R. , Rego Carla M. D. , Gloria David A. , De Oliveira Fabio R. R. , Paes Juliana M. P. , De Sousa Aline A. , Tokuhashi Tatyana P. , Trindade Lucas S. , Turiel Maíra C. P. , Vasconcelos Erick G. R. , Torres João B. , Cunnigham Colm , Perry Victor H. , Da Costa Vasconcelos Pedro F. , Diniz Cristovam W. P.
Published: July 2010

Environmental and age‐related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic‐like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic‐like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long‐term experience‐induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.
Two types of Ca2+ channel linked to two endocytic pathways coordinately maintain synaptic transmission at the Drosophila synapse
Authors: Kuromi H. , Ueno K. , Kidokoro Y.
Published: July 2010

Endocytosis at the presynaptic terminal is initiated by Ca2+ influx through voltage‐gated Ca2+ channels. At the Drosophila neuromuscular junction, we demonstrated two components of endocytosis linked to distinct Ca2+ channels. A voltage‐gated Ca2+ channel blocker, (R)‐(+)‐Bay K8644 (R‐BayK), selectively blocked one component (R‐BayK‐sensitive component) without affecting exocytosis, while low concentrations of La3+ preferentially depressed the other component (La3+ ‐sensitive component). In a temperature‐sensitive mutant, shibirets, at non‐permissive temperatures, dynamin clusters were found immunohistochemically at the active zone (AZ) during the R‐BayK‐sensitive endocytosis, while they were detected at the non‐AZ during the La3+‐sensitive endocytosis. Immunostaining of the Ca2+ channel α2δ subunit encoded by straightjacket (stj) was found within the AZ, and a mutation in stj depressed the R‐BayK‐sensitive component but enhanced the La3+ ‐sensitive one, indicating that the α2δ subunit is associated with the R‐BayK‐sensitive Ca2+ channel. Filipin bound to the non‐AZ membrane and inhibited the La3+ ‐sensitive component, but not the R‐BayK‐sensitive one. We concluded that the R‐BayK‐sensitive component of endocytosis occurred at the AZ and termed this AZ endocytosis. We also concluded that the La3+ ‐sensitive component occurred at the non‐AZ and termed this non‐AZ endocytosis. These two types of endocytosis were modulated by various drugs towards opposite directions, indicating that they were differentially regulated. During high‐frequency stimulation, AZ endocytosis operated mainly in the early phase, whereas non‐AZ endocytosis operated in the late phase. Thus, intense synaptic transmission is coordinately maintained by synaptic vesicle recycling initiated by Ca2+ influx through the two types of Ca2+ channel.
Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic pain
Authors: Martin Yasmina B. , Malmierca Eduardo , Avendaño Carlos , Nuñez Angel
Published: July 2010

The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI‐IoN) as a facial neuropathic model. Pain‐related behavior of the CCI‐IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low‐threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI‐IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on–off tactile response in neurons recorded after CCI‐IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired‐pulse stimulation was reduced after CCI‐IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI‐IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI‐IoN.
Developmental increase in D1‐like dopamine receptor‐mediated inhibition of glutamatergic transmission through P/Q‐type channel regulation in the basal forebrain of rats
Authors: Momiyama Toshihiko
Published: July 2010

Whole‐cell patch‐clamp recordings of non‐N‐methyl‐d‐aspartate glutamatergic excitatory postsynaptic currents (EPSCs) were carried out from cholinergic neurons in slices of basal forebrain (BF) of developing rats aged 21–42 postnatal days to elucidate postnatal developmental change in Ca2+ channel subtypes involved in the transmission as well as that in dopamine D1‐like receptor‐mediated presynaptic inhibition. The amplitude of EPSCs was inhibited by bath application of ω‐conotoxin GVIA (ω‐CgTX; 3 μm) or ω‐agatoxin‐TK (ω‐Aga‐TK; 200 nm) throughout the age range examined, suggesting that multiple types of Ca2+ channel are involved in the transmission. The EPSC fraction reduced by ω‐CgTX decreased with age, whereas that reduced by ω‐Aga‐TK increased. Inhibition of the EPSCs by a D1‐like receptor agonist, SKF 81297 (SKF; 30 μm) increased with age in parallel with the increase in ω‐Aga‐TK‐induced inhibition. An activator of the adenylyl cyclase (AC) pathway, forskolin (FK; 10 μm) inhibited the EPSCs, and FK‐induced inhibition also increased with age in parallel with the increase in SKF‐induced inhibition. Throughout the age range examined, SKF showed no further inhibitory effect on the EPSCs after ω‐Aga‐TK‐ or FK‐induced effect had reached steady‐state. These findings suggest that D1‐like receptor‐mediated presynaptic inhibition of glutamate release onto cholinergic BF neurons increases with age, and that the change is coupled with a developmental increase in the contribution of P/Q‐type Ca2+ channels as well as a developmental increase in AC pathway contribution.
Stability of subicular place fields across multiple light and dark transitions
Authors: Brotons‐Mas Jorge R. , Montejo Noelia , O’Mara Shane M. , Sanchez‐Vives Maria V.
Published: July 2010

Although hippocampal CA1 place cells can be strongly modulated by visual inputs, the effect of visual modulation on place cells in other areas of the hippocampal formation, such as the subiculum, has been less extensively explored. Here, we investigated the role of visual inputs on the activity of subicular place cells by manipulating ambient light levels while freely‐moving rats foraged for food. Rats were implanted with tetrodes in the dorsal subiculum and units were recorded while the animal performed a pellet‐chasing task during multiple light‐to‐dark and dark‐to‐light transitions. We found that subicular place fields presented a somewhat heterogeneous response to light–dark transitions, with 45% of pyramidal units showing stable locational firing across multiple light–dark–light transitions. These data suggest that visual inputs may participate in spatial information processing by the subiculum. However, as a plurality of units was stable across light–dark transitions, we suggest that the subiculum supports, probably in association with the grid cells of the entorhinal cortex, the neurocognitive processing underlying path integration.
Night‐time neuronal activation of Cluster N in a day‐ and night‐migrating songbird
Authors: Zapka Manuela , Heyers Dominik , Liedvogel Miriam , Jarvis Erich D. , Mouritsen Henrik
Published: July 2010

Magnetic compass orientation in a night‐migratory songbird requires that Cluster N, a cluster of forebrain regions, is functional. Cluster N, which receives input from the eyes via the thalamofugal pathway, shows high neuronal activity in night‐migrants performing magnetic compass‐guided behaviour at night, whereas no activation is observed during the day, and covering up the birds’ eyes strongly reduces neuronal activation. These findings suggest that Cluster N processes light‐dependent magnetic compass information in night‐migrating songbirds. The aim of this study was to test if Cluster N is active during daytime migration. We used behavioural molecular mapping based on ZENK activation to investigate if Cluster N is active in the meadow pipit (Anthus pratensis), a day‐ and night‐migratory species. We found that Cluster N of meadow pipits shows high neuronal activity under dim‐light at night, but not under full room‐light conditions during the day. These data suggest that, in day‐ and night‐migratory meadow pipits, the light‐dependent magnetic compass, which requires an active Cluster N, may only be used during night‐time, whereas another magnetosensory mechanism and/or other reference system(s), like the sun or polarized light, may be used as primary orientation cues during the day.
Neural correlates of binaural masking level difference in the inferior colliculus of the barn owl (Tyto alba)
Authors: Asadollahi Ali , Endler Frank , Nelken Israel , Wagner Hermann
Published: July 2010

Humans and animals are able to detect signals in noisy environments. Detection improves when the noise and the signal have different interaural phase relationships. The resulting improvement in detection threshold is called the binaural masking level difference. We investigated neural mechanisms underlying the release from masking in the inferior colliculus of barn owls in low‐frequency and high‐frequency neurons. A tone (signal) was presented either with the same interaural time difference as the noise (masker) or at a 180° phase shift as compared with the interaural time difference of the noise. The changes in firing rates induced by the addition of a signal of increasing level while masker level was kept constant was well predicted by the relative responses to the masker and signal alone. In many cases, the response at the highest signal levels was dominated by the response to the signal alone, in spite of a significant response to the masker at low signal levels, suggesting the presence of occlusion. Detection thresholds and binaural masking level differences were widely distributed. The amount of release from masking increased with increasing masker level. Narrowly tuned neurons in the central nucleus of the inferior colliculus had detection thresholds that were lower than or similar to those of broadly tuned neurons in the external nucleus of the inferior colliculus. Broadly tuned neurons exhibited higher masking level differences than narrowband neurons. These data suggest that detection has different spectral requirements from localization.
Unitized representation of paired objects in area 35 of the macaque perirhinal cortex
Authors: Fujimichi Ryoko , Naya Yuji , Koyano Kenji W. , Takeda Masaki , Takeuchi Daigo , Miyashita Yasushi
Published: July 2010

The perirhinal cortex, which is critical for long‐term stimulus–stimulus associative memory, consists of two cytoarchitectonically distinct subdivisions: area 35 (A35) and area 36 (A36). Previous electrophysiological studies suggested that macaque A36 is involved in both association and retrieval processes during a visual pair‐association task. However, the neuronal properties of macaque A35 have never been examined because A35 is located in a very narrow region, which makes it difficult to systematically record single‐unit activity from there. In the present study, we overcame this technical difficulty for targeting A35 by combining magnetic resonance imaging‐guided in‐vivo localization with postmortem histological localization. This two‐track approach enabled us to record from 181 A35 neurons in two macaque monkeys while they performed a pair‐association task. Among these neurons, 64 showed stimulus‐selective responses during the cue period (cue‐selective neurons), whereas 18 did during the delay period (delay‐selective neurons). As in A36, the responses of cue‐selective neurons in A35 to paired associates were correlated. In both areas, these correlations were stronger in neurons showing delay selectivity than in those without delay selectivity. Notably, delay‐selective neurons in A35 responded similarly to the optimal stimulus and its paired associate, whereas delay‐selective neurons in A36 discriminated between them. However, these neurons in both areas discriminated the primary pair, consisting of the optimal stimulus and its paired associate, from other pairs, indicating that selectivity across pairs was maintained between the two areas. These results suggest that delay‐selective neurons in A35 represent these paired stimuli as a single unitized item rather than two associated items.
Toxic cascades: multiple anthropogenic stressors have complex and unanticipated interactive effects on temperate reefs
Authors: Shears Nick T. , Ross Philip M.
Published: July 2010

Ecology Letters (2010) 13: 1149–1159

In a changing environment multiple anthropogenic stressors can have novel and non‐additive effects on interacting species. We investigated the interactive effects of fishing and harmful algal blooms on the predator‐sea urchin‐macroalgae trophic cascade. Fishing of urchin predators had indirect negative effects on macroalgae, whereas blooms of epi‐benthic dinoflagellates (Ostreopsis siamensis) were found to have strong negative effects on urchins and indirect positive effects on macroalgae. Based on these opposing effects, blooms were expected to counteract the cascading effects of fishing. However, a large bloom of Ostreopsis led to greater divergence in macroalgae abundance between reserve and fished sites, as urchins declined at reserve sites but remained stable at fished sites. This resulted from enhanced predation rates on bloom‐affected urchins at reserve sites rather than direct lethal effects of Ostreopsis on urchins. We argue that interacting stressors can facilitate or attenuate trophic cascades depending on stressor intensity and complex non‐lethal interactions.
Controversial aspects of rectal cancer surgery following preoperative chemoradiation
Authors: Artioukh D. Y.
Published: July 2010

The role of surgery in the loco‐regional control of adenocarcinoma of the rectum is being increasingly challenged by the good response rates of neoadjuvant oncological treatment. This review represents an opinion paper outlining well‐established choices and new trends in surgical intervention, unresolved difficulties of local and regional staging of rectal malignancy and accurate assessment of tumour response to preoperative downstaging chemoradiation. The influence of preoperative chemoradiation on subsequent surgical strategy is discussed highlighting several controversial aspects of surgical management both when the tumour fails to respond and appears to be irresectable and when complete clinical response is observed.
Cardiopulmonary bypass and renal cell carcinoma with level IV tumour thrombus: can deep hypothermic circulatory arrest limit perioperative mortality?
Authors: Shuch Brian , Crispen Paul L. , Leibovich Bradley C. , LaRochelle Jeff C. , Pouliot Frederic , Pantuck Allan J. , Liu Weiqing , Crepel Maxime , Schuckman Anne , Rigaud Jerome , Bouchot Oliver , Patard Jean‐Jacques , Skinner Donald , Belldegrun Arie S. , Blute Michael L.
Published: July 2010

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

Removal of a renal cell carcinoma with a level IV tumour thrombus is a challenging surgery and generally is performed in a tertiary care centre. Performing these cases generally requires a multi‐disciplinary approach consisting of urological and vascular/cardiovascular surgeons.

This study sheds light on the high surgical morbidity and mortality of these cases even at experienced centres. For patients requiring cardiopulmonary bypass, approximately 20% may not survive. In these challenging surgeries, deep hypothermic circulatory arrest may limit mortality and further studies should investigate the protective effect of this modality.

OBJECTIVE

• To review experience with nephrectomy/thrombectomy for a renal cell carcimoma (RCC) with a level IV tumour thrombus and to evaluate the benefit of deep hypothermic circulatory arrest (DHCA) with cardiopulmonary bypass (CPBP).

PATIENTS AND METHODS

• A multi‐institutional retrospective database was created to assess the outcomes of surgery for RCC and associated level IV tumour thrombus from 1983 to 2007. Patients were identified based on radiographic records/operative findings.

• Only cases using CPBP were analysed. Clinicopathological and operative characteristics including use of DHCA were recorded.

• Overall survival (OS) for all patients and by use of DHCA was assessed. Comparisons of clinical and operative characteristics by use of DHCA were performed.

• A Cox regression model determined predictors of perioperative/in‐hospital mortality.

RESULTS

• In all, 63 patients underwent resection with CPBP; overall perioperative mortality was 22.2%.

• There were no significant differences in clinicopathological characteristics, operative duration, estimated blood loss, transfusions, and hospital stay by use of DHCA.

• Perioperative mortality rate was lower in patients undergoing DHCA (8.3% vs 37.5%, P= 0.006).

• The median OS was longer for the patients undergoing DHCA (15.8 vs 7.7 months); however, this failed to reach statistical significance (P= 0.357).

• On multivariate analysis, age of >60 years (hazard ratio [HR] 6.7, 95% confidence interval [CI] 1.5–31.1, P= 0.015) and the use of DHCA (HR 0.13, 95% CI 0.036–0.51, P= 0.003) were independent predictors of perioperative mortality.

CONCLUSIONS

• Radical nephrectomy and level IV tumour thrombectomy is associated with significant mortality.

• The use of DHCA does not appear to adversely affect operative characteristics and may limit perioperative mortality.

• Further prospective studies should be performed to confirm the benefit of DHCA.
Fear of hypoglycaemia in adults with Type 1 diabetes
Authors: Anderbro T. , Amsberg S. , Adamson U. , Bolinder J. , Lins P.‐E. , Wredling R. , Moberg E. , Lisspers J. , Johansson U.‐B.
Published: July 2010

Diabet. Med. 27, 1151–1158 (2010)

Aims  The aim of this study was to examine the fear of hypoglycaemia and its association with demographic and disease‐specific variables in a large and unselective population of adult patients with Type 1 diabetes.

Methods  Questionnaires were sent by post to all patients with Type 1 diabetes who were identified in the local diabetes registries of two hospitals in Stockholm, Sweden (n = 1387). Fear of hypoglycaemia was measured using the Swedish Hypoglycaemia Fear Survey, the Worry subscale and the Aloneness subscale. Demographic variables and disease‐specific factors were collected from patients’ self reports and medical records. Univariate analysis and multiple stepwise linear regression analysis were used in the statistical analyses of the data.

Results  Seven hundred and sixty‐four (55%) patients participated in the study (mean age 43.3 years and mean HbA1c 7.0%, normal < 5.0%). The Hypoglycaemia Fear Survey ‐ Worry subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, hypoglycaemic symptoms during hyperglycaemia and hypoglycaemic unawareness. The Hypoglycaemia Fear Survey ‐ Aloneness subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, frequency of mild hypoglycaemia, HbA1c, hypoglycaemic unawareness and visits to the emergency room because of severe hypoglycaemia. Fear of hypoglycaemia proved to be more prevalent in females and indicated a different pattern between genders in relation to factors associated with fear of hypoglycaemia.

Conclusions  This study identifies the frequency of severe hypoglycaemia as the most important factor associated with fear of hypoglycaemia. Moreover, for the first time, we document gender differences in fear of hypoglycaemia, suggesting that females are more affected by fear of hypoglycaemia than men.
Glycated haemoglobin and blood pressure‐lowering effect of cinnamon in multi‐ethnic Type 2 diabetic patients in the UK: a randomized, placebo‐controlled, double‐blind clinical trial
Authors: Akilen R. , Tsiami A. , Devendra D. , Robinson N.
Published: July 2010

Diabet. Med. 27, 1159–1167 (2010)

Aims  To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes.

Methods  58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks.

Results  After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups.

Conclusions  Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus.
Prophylactic use of anti‐emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open‐label, parallel‐group, single‐dose study in healthy subjects
Authors: Ellero C. , Han J. , Bhavsar S. , Cirincione B. B. , DeYoung M. B. , Gray A. L. , Yushmanova I. , Anderson P. W.
Published: July 2010

Diabet. Med. 27, 1168–1173 (2010)

Aims  Transient nausea and, to a lesser extent, vomiting are common adverse effects of exenatide that can be mitigated by dose titration and usually do not result in treatment discontinuation. This retrospective analysis of data from a phase 1, open‐label, parallel‐group, single‐dose study in healthy subjects evaluated the effect of oral anti‐emetics on exenatide‐associated nausea and vomiting and on the pharmacokinetics of exenatide.

Methods  A single subcutaneous dose (10 μg) of exenatide was administered to 120 healthy subjects (19–65 years, BMI 23–35 kg/m2). Incidences of nausea and vomiting were compared between 60 subjects premedicated with two oral anti‐emetics 30 min before the exenatide dose and 60 non‐premedicated subjects. Similarly, the area under the concentration‐time curve (AUC) and the maximum observed concentration (Cmax) of plasma exenatide concentrations over 8 h post‐dose were compared.

Results  Among all subjects [61% male, 32 ± 12 years, body mass index (BMI) 29.1 ± 3.4 kg/m2 (mean ± sd)], mild to moderate nausea was the most frequent adverse event after exenatide dosing. Vomiting was also observed. Subjects premedicated with anti‐emetics experienced significantly less nausea and vomiting (16.7 and 6.7%, respectively) vs. non‐premedicated subjects (61.7 and 38.3%, respectively; P‐value < 0.0001 for both nausea and vomiting). The mean area under the concentration‐time curve and the maximum observed concentration AUC and Cmax of plasma exenatide concentrations during 8 h post‐dose were not significantly different between groups.

Conclusion  Administration of oral anti‐emetics before a single 10‐μg exenatide dose was associated with significant reductions in treatment‐emergent nausea and vomiting, with no discernible effect on the pharmacokinetics of exenatide. Use of anti‐emetic therapy may provide a short‐term strategy to minimize the nausea and vomiting associated with exenatide treatment.
Reflecting team processes in family therapy: a search for research
Authors: Willott Sara , Hatton Terry , Oyebode Jan
Published: July 2010

Tom Andersen's Reflecting Team approach is widely (and creatively) employed in family therapy. Despite continuing enthusiasm for the practice, however, there are few journal articles reporting empirical research and only one (now dated) review of the literature. After defining reflecting team processes through practices that are embedded in particular approaches to knowledge construction and theoretical interpretation, we offer an overview of the empirical research found in our search of the literature. In the second half of this article we ask why there is so little existing research in this area. Various possible explanations are explored and future directions proposed. We conclude that a dialogue around the complex interweaving of practice, theory and research (that is, praxis) would be a helpful overall stance to adopt in relation to future work in this area.
Health and social impacts of a flood disaster: responding to needs and implications for practice
Authors: Carroll Bob , Balogh Ruth , Morbey Hazel , Araoz Gonzalo
Published: July 2010

Carlisle in northwest England suffered its worse floods for more than 180 years in 2005. A study, reported here, was undertaken to assess the health and social impacts of these floods via in‐depth, taped individual and focus‐group interviews with people whose homes had been flooded and with agency workers who helped them. Respondents spoke of physical health ailments, psychological stress, water health‐and‐safety issues related to the floods, and disputes with insurance and construction companies, which they felt had caused and exacerbated psychological health problems. Support workers also suffered from psychological stress. Furthermore, it was found that people had low expectations of a flood and were not prepared. The findings are presented in five sections covering flood risk awareness, water contamination issues, physical health, mental health, and impact on frontline support workers. The discussion focuses on the implications of the findings for policy and practice vis‐à‐vis psychological health provision, contamination issues, training and support for frontline support workers, matters relating to restoration, and preparation for flooding.
Disaster risk from a macroeconomic perspective: a metric for fiscal vulnerability evaluation
Authors: Cardona Omar D. , Ordaz Mario G. , Marulanda Mabel C. , Carreño Martha L. , Barbat Alex H.
Published: July 2010

The Disaster Deficit Index (DDI) measures macroeconomic and financial risk in a country according to possible catastrophic scenario events. Extreme disasters can generate financial deficit due to sudden and elevated need of resources to restore affected inventories. The DDI captures the relationship between the economic loss that a country could experience when a catastrophic event occurs and the availability of funds to address the situation. The proposed model utilises the procedures of the insurance industry in establishing probable losses, based on critical impacts during a given period of exposure; for economic resilience, the model allows one to calculate the country's financial ability to cope with a critical impact. There are limitations and costs associated with access to resources that one must consider as feasible values according to the country's macroeconomic and financial conditions. This paper presents the DDI model and the results of its application to 19 countries of the Americas and aims to guide governmental decision‐making in disaster risk reduction.
A systematic review of environmental factors and obesogenic dietary intakes among adults: are we getting closer to understanding obesogenic environments?
Authors: Giskes K. , van Lenthe F. , Avendano‐Pabon M. , Brug J.
Published: July 2010

This study examined whether physical, social, cultural and economical environmental factors are associated with obesogenic dietary behaviours and overweight/obesity among adults. Literature searches of databases (i.e. PubMed, CSA Illumina, Web of Science, PsychInfo) identified studies examining environmental factors and the consumption of energy, fat, fibre, fruit, vegetables, sugar‐sweetened drinks, meal patterns and weight status. Twenty‐eight studies were in‐scope, the majority (n= 16) were conducted in the USA. Weight status was consistently associated with the food environment; greater accessibility to supermarkets or less access to takeaway outlets were associated with a lower BMI or prevalence of overweight/obesity. However, obesogenic dietary behaviours did not mirror these associations; mixed associations were found between the environment and obesogenic dietary behaviours. Living in a socioeconomically‐deprived area was the only environmental factor consistently associated with a number of obesogenic dietary behaviours. Associations between the environment and weight status are more consistent than that seen between the environment and dietary behaviours. The environment may play an important role in the development of overweight/obesity, however the dietary mechanisms that contribute to this remain unclear and the physical activity environment may also play an important role in weight gain, overweight and obesity.
Is (Institutional) Shareholder Activism New? Evidence from UK Shareholder Coalitions in the Pre‐Cadbury Era
Authors: Crespi Rafel , Renneboog Luc
Published: July 2010

Manuscript Type: Empirical

Research Question/Issue: Does recent institutional shareholder activism have a precedent in the form of (ad hoc) shareholder coalitions that force the manager to leave poorly performing companies?

Research Findings/Insights: To address the above question, we investigate whether or not shareholder voting coalitions disciplined managers in the pre‐Cadbury era. We find that the voting power held (Shapley values) by financial institutions (mainly, the insurance companies) are positively related to executive director turnover. Coalitions of industrial and commercial companies with strong relative voting power penalize poorly performing managers. In contrast, coalitions of executive directors are able to resist board restructuring. Finally, we a strong relation between top management substitution and high debt levels, especially in companies in need of refinancing.

Theoretical/Academic Implications: We use Shapley values which are power indices developed in the field of (oceanic) game theory in order to capture the relative voting power of a shareholder in all possible shareholder coalitions. A shareholder who is pivotal in many potential coalitions is hence powerful and received a high Shapley value. The use of such power indices yield much stronger results in our models that any of the other measures traditionally used in corporate governance research to measure voting power/ownership concentration. This methodology enables us to draw clear conclusions on the existence of voting coalitions.

Practitioner/Policy Implications: This paper shows that voting coalition of shareholders can be instrumental in bringing about change in poorly performing companies.
Simultaneous Inference of Linear Models with Time Varying Coefficients
Authors: Zhou Zhou , Wu Wei Biao
Published: July 2010

The paper considers construction of simultaneous confidence tubes for time varying regression coefficients in functional linear models. Using a Gaussian approximation result for non-stationary multiple time series, we show that the constructed simultaneous confidence tubes have asymptotically correct nominal coverage probabilities. Our results are applied to the problem of testing whether the regression coefficients are of certain parametric forms, which is a fundamental problem in the inference of functional linear models. As an application, we analyse an environmental data set and study the association between levels of pollutants and hospital admissions.