bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observational study of iron overload as assessed by magnetic resonance imaging in an adult population of transfusion‐dependent patients with β thalassaemia: significant association between low cardiac T2* < 10 ms and cardiac events
Authors: Patton N. , Brown G. , Leung M. , Bavishi K. , Taylor J. , Lloyd J. , Lee S.‐H. , Tay L. , Worthley S. 
Published: May 2009

AbstractBackground: Thalassaemia major patients usually die from cardiac haemosiderosis. Improved strategies are required to modify this risk.Aims: To assess the significance of cardiac iron overload in patients with β thalassaemia.Method: Observational study of cardiac iron overload as assessed by magnetic resonance imaging (MRI) cardiac T2* relaxometry in 30 adult patients with transfusion‐dependent β thalassaemia.Results: 11/30 patients (37%) had cardiac T2* < 10 ms, 8/30 (27%) in range 10–20 ms and 11/30 (37%) > 20 ms. There was significant inverse correlation between T2* values and values for serum ferritin (SF) and liver iron concentration (LIC) and positive correlation with left ventricular ejection fraction (LVEF). Median LVEF values were 49% in patients with T2* < 10 ms and 58% in patients with T2* > 10 ms (P= 0.02). Very low T2* values <10 ms were strongly associated with the occurrence of cardiac events (congestive heart failure, arrhythmia, cardiac death): occurring in 5/11 patients with T2* < l0 ms and in 0/19 in patients with T2* > 10 ms (P= 0.003 Fisher's exact test; P= 0.002 log rank Kaplan‐Meier time to event analysis). There was no significant association between T2* < 10 ms or cardiac events and traditional measures of iron overload, such as SF levels >2500 µg/L and LIC (evaluated at thresholds of >7 or >15 mg/g dry weight).Conclusion: Very low cardiac T2* values <10 ms are common in adults with β thalassaemia and are significantly associated with risk of cardiac events. This permits the use of individually targeted chelation strategies which are more effective in removing cardiac iron.
Molecular architecture of endocannabinoid signaling at nociceptive synapses mediating analgesia
Authors: Nyilas Rita , Gregg Laura C. , Mackie Ken , Watanabe Masahiko , Zimmer Andreas , Hohmann Andrea G. , Katona István 
Published: May 2009

AbstractCannabinoid administration suppresses pain by acting at spinal, supraspinal and peripheral levels. Intrinsic analgesic pathways also exploit endocannabinoids; however, the underlying neurobiological substrates of endocannabinoid‐mediated analgesia have remained largely unknown. Compelling evidence shows that, upon exposure to a painful environmental stressor, an endocannabinoid molecule called 2‐arachidonoylglycerol (2‐AG) is mobilized in the lumbar spinal cord in temporal correlation with stress‐induced antinociception. We therefore characterized the precise molecular architecture of 2‐AG signaling and its involvement in nociception in the rodent spinal cord. Nonradioactivein situhybridization revealed that dorsal horn neurons widely expressed the mRNA of diacylglycerol lipase‐alpha (DGL‐α), the synthesizing enzyme of 2‐AG. Peroxidase‐based immunocytochemistry demonstrated high levels of DGL‐α protein and CB1cannabinoid receptor, a receptor for 2‐AG, in the superficial dorsal horn, at the first site of modulation of the ascending pain pathway. High‐resolution electron microscopy uncovered postsynaptic localization of DGL‐α at nociceptive synapses formed by primary afferents, and revealed presynaptic positioning of CB1on excitatory axon terminals. Furthermore, DGL‐α in postsynaptic elements receiving nociceptive input was colocalized with metabotropic glutamate receptor 5 (mGluR5), whose activation induces 2‐AG biosynthesis. Finally, intrathecal activation of mGluR5at the lumbar level evoked endocannabinoid‐mediated stress‐induced analgesia through the DGL–2‐AG–CB1pathway. Taken together, these findings suggest a key role for 2‐AG‐mediated retrograde suppression of nociceptive transmission at the spinal level. The striking positioning of the molecular players of 2‐AG synthesis and action at nociceptive excitatory synapses suggests that pharmacological manipulation of spinal 2‐AG levels may be an efficacious way to regulate pain sensation.
Inactivation of lateral connections in cat area 17
Authors: Girardin Cyrille C. , Martin Kevan A. C. 
Published: May 2009

AbstractExcitatory synapses arising from local neurons in the cat visual cortex are much more numerous than the thalamocortical synapses, which provide the primary sensory input. Many of these local circuit synapses are involved in the connections between cortical layers, but lateral connections within layers provide a major component of the local circuit synapses. We tested the influence of these lateral connections in the primary visual cortex of cats by inactivating small patches of cortex about 450 μm lateral from the recording pipette. By use of the neurotransmitter γ‐aminobutyric acid (GABA), small patches of cortex were inhibited and released from inhibition in seconds. Orientation tuning curves derived from responses to oriented drifting gratings were obtained during short control periods interleaved with periods of GABA inactivation. About 30% of the cells (18/62, recorded in all layers) changed their orientation tuning when a small portion of their lateral input was silenced. There was no broadening of the orientation tuning curve during lateral inactivation. Instead, the recorded cells shifted their preferred orientation towards the orientation of the inactivated site. One explanation is that the GABA inactivation alters the balance of excitatory and inhibitory inputs to a cell, which results in a shift of the cell’s preferred orientation.
Dissociation of attention and intention in human posterior parietal cortex: an fMRI study
Authors: Hu Siyuan , Bu Yong , Song Yiying , Zhen Zonglei , Liu Jia 
Published: May 2009

AbstractIn natural environments, the orienting of attention to an object of interest occurs jointly with selecting it as a potential target for action. This coupling of perceptual selection and motor planning has led to ‘the premotor theory of attention’, which argues that attention and intention share the same neural mechanism. Here we used fMRI to test this hypothesis by examining neural activity in the temporal parietal junction (TPJ) and intraparietal sulcus (IPS) of the posterior parietal cortex (PPC) while subjects searched for a target among distractors with the presence of color singletons. Task‐relevant salience of stimuli and the variability of response time were used to characterize the behavior of attention and intention components of the visuomotor transformation performed in these two cortical regions, respectively. We found that TPJ responses were significantly higher when the color singletons were distractors (vs. targets), suggesting that the TPJ was involved in attentional control of interference from task‐irrelevant but salient stimuli. In contrast, signals in the IPS were closely related to the variability of response time, with a larger BOLD response associated with longer RTs, suggesting that the IPS plays a pivotal role in intention by translating encoded information into action through evidence accumulation. Our data help to specify the functional division of labor between the IPS and TPJ and to further dissociate process components in visual search.
The periaqueductal grey modulates sensory input to the cerebellum: a role in coping behaviour?
Authors: Cerminara Nadia L. , Koutsikou Stella , Lumb Bridget M. , Apps Richard 
Published: May 2009

AbstractThe paths that link the periaqueductal grey (PAG) to hindbrain motor circuits underlying changes in behavioural responsiveness to external stimuli are unknown. A major candidate structure for mediating these effects is the cerebellum. The present experiments test this directly by monitoring changes in size of cerebellar responses evoked by peripheral stimuli following activation of the PAG. In 22 anaesthetized adult Wistar rats, climbing fibre field potentials were recorded from the C1 zone in the paramedian lobule and the copula pyramidis of the cerebellar cortex evoked, respectively, by electrical stimulation of the ipsilateral fore‐ and hindlimb. An initial and a late response were attributable to activation of Aβ and Aδ peripheral afferents respectively (hindlimb onset latencies 16.9 and 23.8 ms). Chemical stimulation at physiologically‐identified sites in the ventrolateral PAG (a region known to be associated with hyporeactive immobility) resulted in a significant reduction in size of both the Aβ and Aδ evoked field potentials (mean reduction relative to control ± SEM, 59 ± 7.5 and 66 ± 11.9% respectively). Responses evoked by electrical stimulation of the dorsal or ventral funiculus of the spinal cord were also reduced by PAG stimulation, suggesting that part of the modulation may occur at supraspinal sites (including at the level of the inferior olive). Overall, the results provide novel evidence of descending control into motor control centres, and provide the basis for future studies into the role of the PAG in regulating motor activity in different behavioural states and in chronic pain.
Diabetes specialist nurses and role evolvement: a survey by Diabetes UK and ABCD of specialist diabetes services 2007
Authors: James J. , Gosden C. , Winocour P. , Walton C. , Nagi D. , Turner B. , Williams R. , Holt R. I. G. 
Published: May 2009

AbstractAims  To review the working practices of UK diabetes specialist nurses (DSNs), specific clinical roles, and to examine changes since 2000.Methods  Postal questionnaires were sent to lead DSNs from all identifiable UK diabetes centres (n =  361). Quantitative and qualitative data were collected on the specific clinical roles, employment, and continual professional development of hospital and community DSNs, Nurse Consultants and Diabetes Healthcare Assistants.Results  159 centres (44%) returned questionnaires. 78% and 76% of DSNs plan and deliver education sessions compared with 13% in 2000 with a wider range of topics and with less input from medical staff. 22% of DSNs have a formal role in diabetes research compared with 48% in 2000. 49% of Hospital DSNs, 56% of Community DSNs and 66% of Nurse Consultants are involved in prescribing. 55% of DSNs carry out pump training, 72% participate in ante‐natal and 27% renal clinics. 90% of services have independent diabetes nurse‐led clinics. 93% of services have a dedicated Paediatric DSN. The mean number of children under the care of each PDSN is 109 (mode 120), which exceeds Royal College of Nursing recommendations. 48% of DSNs have protected time for continuing professional development of staff and 15% have a protected budget. One third of DSNs are on short‐term contracts funded by external sources.Conclusions  The DSN role has evolved since 2000 to include complex service provision and responsibilities including specialist clinics, education of healthcare professionals and patients. The lack of substantive contracts and protected study leave may compromise these roles in the future.
Is breech presentation a risk factor for cerebral palsy? A Norwegian birth cohort study
Authors: ANDERSEN GURO L , IRGENS LORENTZ M , SKRANES JON , SALVESEN KJELL Å , MEBERG ALF , VIK TORSTEIN 
Published: May 2009

Aim  To study whether breech presentation is a risk factor for cerebral palsy (CP).Methods  Perinatal data from 177 272 children born in breech or vertex presentation in Norway during 1996 to 1998 were retrieved from the Medical Birth Registry of Norway. Data were collected between 1 January 2003 and 31 March 2006. Data on 245 children with CP were recorded in the Norwegian Cerebral Palsy Registry. Odds ratios (OR) with 95% confidence intervals (CI) for CP among children born in breech compared with vertex presentation were calculated. Confounding was addressed in logistic regression and stratified analyses.Results  Among the 245 children with CP (46.5% females and 53.5% males), 31% had unilateral, 49% bilateral, 7% dyskinetic, and 5% the ataxic subtype, and 8% of cases were unclassified. Among children born in breech, the OR for CP was 3.6 (95% CI 2.4–5.3). The increased risk was reduced when adjusted for preterm birth, plurality, and smallness for gestational age. Among singletons born in breech by vaginal delivery at term, the OR for CP was 3.9 (95% CI 1.6–9.7). Severity or subtype of CP did not differ between breech and vertex presentation.Interpretation  Breech delivery is a significant risk factor for CP, in particular among singletons born by vaginal delivery at term.
Intake of vitamin C and E in pregnancy and risk of pre‐eclampsia: prospective study among 57 346 women
Authors: Klemmensen ÅK , Tabor A , Østerdal ML , Knudsen VK , Halldorsson TI , Mikkelsen TB , Olsen SF 
Published: May 2009

Objective  It has been suggested that vitamin C, alone or in combination with vitamin E, may protect against pre‐eclampsia, whereas the safety of high‐dose vitamin E supplements has been questioned. We investigated dietary intakes of vitamins C and E to see if they correlated with the incidence of pre‐eclampsia.Design  Prospective cohort study.Setting  The Danish National Birth Cohort; a population‐based pregnancy cohort; analyses were based on 57 346 pregnancies.Methods  Vitamin intake was estimated from a food frequency questionnaire completed in gestational week 25, recording intake from diet and supplements during the previous four weeks. Pre‐eclampsia diagnoses were obtained from the Danish National Patient Registry; we worked with two entities, ‘pre‐eclampsia (all types)’ and ‘severe pre‐eclampsia/eclampsia/HELLP’. We adjusted for confounding factors by logistic regression.Main outcome measures  A small increase in the incidence of severe disease was also seen in the group of women (64, n = 49 373) with a high intake of vitamin E from supplements and dietary sources.Results  The incidence of ‘pre‐eclampsia (all types)’ did not correlate with dietary vitamin C and E intake. There was a decreasing trend (P = 0.01) in the incidence of ‘severe pre‐eclampsia/eclampsia/HELLP’ with increasing dietary vitamin C intake; with an intake of 130–170 mg/day as reference, odds ratios ranged from 1.21 (95% confidence interval 0.83 to 1.75) for an intake below 70 mg/day to 0.70 (0.40 to 1.23) for an intake exceeding 275 mg/day (total n = 57 346). For vitamin E intake aggregated from diet and supplements (n = 49 373), with an intake of 10.5–13.5 mg/day as reference, the ‘severe pre‐eclampsia/eclampsia/HELLP’ odds ratio was 1.46 (1.02 to 2.09) for an intake exceeding 18 mg/day.Conclusions  Low dietary intake of vitamin C was associated with a trend towards an increased incidence of either severe pre‐eclampsia, eclampsia or HELLP. A small increase in the incidence of severe disease was also seen in the group of women with a high intake of vitamin E from supplements and dietary sources.
The effect of exclusion of cases with unrecorded best estimate of gestational age on the estimates of preterm birth rate
Authors: Balchin I , Whittaker JC , Lamont RF , Steer PJ 
Published: May 2009

Objectives  To investigate the effect of excluding cases with unrecorded best estimate of gestational age at birth on pregnancy outcome reporting and to determine the reasons for unrecorded gestational age data.Design  Prospective study.Setting  Fifteen maternity units in North West London.Population  497 105 women who booked for antenatal care from 1988 to 1998.Method  Multiple logistic regression analysis.Main outcome measures  Preterm birth rate of, and the factors associated with, cases with unrecorded best estimate of gestational age at birth.Results  Of the 53 981 cases with an unrecorded best estimate of gestational age at birth, by using additional data, it was possible to compute a new best estimate of gestational age in 80%. In this latter group, the preterm birth rate was 42% (95% CI 41.5–42.6). The corrected, overall preterm birth rate in North West London (9.8%, 9.7–9.9) was higher than the original estimate (7.6%, 7.5–7.7), which included only cases with recorded data on gestational age at birth. The most significant factors associated with an unrecorded gestational age were no ultrasound scan (OR 49, P < 0.001), and preterm birth <31 weeks (OR 30, P < 0.001).Conclusions  The incidence of preterm birth are likely to be under‐reported in studies where only cases with readily available gestational age data are included. In routinely collected maternity data, human omission is an important contributing factor for an unrecorded best estimate of gestational age at birth. This is associated with the urgent transfer of babies to the neonatal intensive care unit.
The effects of obesity and HER‐2 polymorphisms as risk factors for endometrial cancer in Korean women
Authors: Tong S‐Y , Ha S‐Y , Ki K‐D , Lee J‐M , Lee S‐K , Lee K‐B , Kim M‐K , Cho C‐H , Kwon S‐Y 
Published: May 2009

Objective  To evaluate the relationship between single nucleotide polymorphisms (SNPs) in the HER‐2 gene, body mass index (BMI) and the risk of endometrial cancer.Design  Case–control study.Setting  Medical centres in Korea.Sample  DNA samples and medical histories were obtained from 125 endometrial cancer cases and 302 controls.Methods  The genotypes evaluated in HER‐2 at positions –423, –655, –776, –857, –1170, –1177, –1253 of the coding region and two SNPs located in an intron by SNP‐IT assay using SNPstream Ultra–high throughput system.Main outcome measures  Odd ratio for endometrial cancer associated with HER‐2 polymorphisms and BMI.Results  Cases had a significantly higher BMI than controls and the obese subjects had a 2.65‐fold increased risk for endometrial cancer. However, HER‐2 polymorphism was not associated significantly with the risk of endometrial cancer. Subjects with BMI ≥ 25 kg/m2 who carried rs1801200 AA, rs1801200 GA/GG, rs1810132 CT/CC, rs2517951 CT/TT and rs1058808 CG/GG genotype had significantly increased risk of endometrial cancer than subjects with a normal BMI (P for linear trend <0.05). However, the risk in the subjects with the variant allele for HER‐2 genotypes did not differ significantly compared to those with homozygous wild‐type allele within specific BMI subgroups.Conclusions  Endometrial cancer risk increased significantly in proportion to BMI. However, HER‐2 polymorphism did not affect significantly on the risk of endometrial cancer.
A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium: follow up at a minimum of 10 years
Authors: Sambrook AM , Bain C , Parkin DE , Cooper KG 
Published: May 2009

Objective  To compare outcomes and further operations at a minimum of 10 years following microwave endometrial ablation (MEATM) or transcervical resection of the endometrium (TCRE).Design  Follow up of a randomised controlled trial using postal questionnaires and operative databank review.Setting  Gynaecology department of a large UK teaching hospital.Main outcome measures  Women’s satisfaction with treatment, menstrual symptoms, changes in health‐related quality of life, and additional treatments received.Results  One‐hundred and eighty‐nine of the original 263 women returned questionnaires (72%) after a minimum of 10 years post‐treatment. Those totally or generally satisfied with treatment numbered 77/129 (60%) in the microwave arm and 70/134 (52%) in the resection arm, the difference is not statistically significant. Bleeding and pain scores were highly significantly reduced and similar following both MEATM and TCRE, achieving amenorrhoea rates of 83 and 88% respectively. The hysterectomy rate after 10 years was significantly different with 22 (17%) in the MEATM and 38 (28%) in the TCRE arm (95% CI: −0.21, −0.13).Conclusions  Both techniques achieve significant and comparable improvements in menstrual symptoms, health‐related quality of life and high rates of satisfaction. With the known operative advantages, lower costs and fewer hysterectomies, it is clear that MEA™ is a more effective and efficient treatment for heavy menstrual loss than TCRE.
Effects of the antipsychotic drug haloperidol on the somastostatinergic system in SH‐SY5Y neuroblastoma cells
Authors: Sánchez‐Wandelmer Jana , Hernández‐Pinto Alberto M. , Cano Sonia , Dávalos Alberto , De La Peña Gema , Puebla‐Jiménez Lilian , Arilla‐Ferreiro Eduardo , Lasunción Miguel A. , Busto Rebeca 
Published: May 2009

AbstractAntipsychotics are established drugs in schizophrenia treatment which, however, are not free of side effects. Lipid rafts are critical for normal brain function. Several G protein‐coupled receptors, such as somatostatin (SRIF) receptors, have been shown to localize to lipid rafts. The aim of this study was to investigate whether haloperidol treatment affects the composition and functionality of lipid rafts in SH‐SY5Y neuroblastoma cells. Haloperidol inhibited cholesterol biosynthesis, leading to a marked reduction in cell cholesterol content and to an accumulation of sterol intermediates, particularly cholesta‐8,14‐dien‐3β‐ol. These changes were accompanied by a loss of flotillin‐1 and Fyn from the lipid rafts. We next studied the functionality of the SRIF receptor. Treatment with haloperidol reduced the inhibitory effect of SRIF on adenylyl cyclase (AC) activity. On the other side, haloperidol decreased basal AC activity but increased forskolin‐stimulated AC activity. Addition of free cholesterol to the culture medium abrogated the effects of haloperidol on lipid raft composition and SRIF signaling whereas the AC response to forskolin remained elevated. The results show that haloperidol, by affecting cholesterol homeostasis, ultimately alters SRIF signaling and AC activity, which might have physiological consequences.
The Gal4/UAS toolbox in zebrafish: new approaches for defining behavioral circuits
Authors: Scott Ethan K. 
Published: May 2009

AbstractOver recent years, several groundbreaking techniques have been developed that allow for the anatomical description of neurons, and the observation and manipulation of their activity. Combined, these approaches should provide a great leap forward in our understanding of the structure and connectivity of the nervous system and how, as a network of individual neurons, it generates behavior. Zebrafish, given their external development and optical transparency, are an appealing system in which to employ these methods. These traits allow for direct observation of fluorescence in describing anatomy and observing neural activity, and for the manipulation of neurons using a host of light‐triggered proteins. Gal4/Upstream Activating Sequence techniques, as they are based on a binary system, allow for the flexible deployment of a range of transgenes in expression patterns of interest. As such, they provide a promising approach for viewing neurons in a variety of ways, each of which can reveal something different about their structure, connectivity, or function. In this study, the author will review recent progress in the development of the Gal4/Upstream Activating Sequence system in zebrafish, feature examples of promising studies to date, and examine how various new technologies can be used in the future to untangle the complex mechanisms by which behavior is generated.