bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of non‐alcoholic fatty liver disease on microalbuminuria in patients with prediabetes and diabetes
Authors: Hwang S. T. , Cho Y. K. , Yun J. W. , Park J. H. , Kim H. J. , Park D. I. , Sohn C. I. , Jeon W. K. , Kim B. I. , Rhee E. J. , Oh K. W. , Lee W. Y. , Jin W.
Published: May 2009

Background: It is unknown whether microalbuminuria is associated with non‐alcoholic fatty liver disease (NAFLD) among patients with prediabetes and type 2 diabetes mellitus (DM). This study investigated the association of NAFLD with microalbuminuria among patients with prediabetes and diabetes.

Methods: We evaluated 1361 subjects who had an abnormal oral glucose tolerance test (OGTT) on routine screening. All participants were divided into two groups, prediabetes and newly diagnosed type 2 DM, and the association of NAFLD with metabolic parameters on microalbuminuria was analysed.

Results: The patients with NAFLD had higher prevalence rates of microalbuminuria (6.3% vs 19%; P= 0.001 in prediabetes, 4.5% vs 32.6%; P < 0.001 in diabetes) and also had a greater albumin‐to‐creatinine ratio (14.6 ± 52.0 µg/mg Cr vs 27.7 ± 63.9 µg/mg Cr; P= 0.051 in prediabetes, 11.4 ± 21.4 µg/mg Cr vs 44.7 ± 76.4 µg/mg Cr; P < 0.001 in diabetes) than those without NAFLD. The logistic regression analysis showed that NAFLD was associated with increased rates of microalbuminuria (odds ratio 3.66; 95% confidence interval (CI) 1.31–10.20, P= 0.013 in prediabetes, odds ratio 5.47; 95% CI 1.01–29.61, P= 0.048 in diabetes), independently of age, sex, body mass index, waist circumference, liver enzymes, lipid profiles, HbA1c, insulin resistance as estimated by homeostasis model assessment, hypertension, smoking status and the metabolic syndrome.

Conclusions: The results of our study revealed a strong relationship between microalbuminuria and NAFLD in the patients with prediabetes and newly diagnosed diabetes. Further studies are required to confirm whether NAFLD is a predictor of the development of microalbuminuria in patients with prediabetes and diabetes.
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

Background: 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

Cannabinoid 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

Excitatory 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

In 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

The 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

Aims  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.
Varieties of Multinationals: Adapting Employment Practices in Central Eastern Europe
Authors: MEARDI GUGLIELMO , MARGINSON PAUL , FICHTER MICHAEL , FRYBES MARCIN , STANOJEVIĆ MIROSLAV , TÓTH ANDRÁS
Published: May 2009

“Home‐country effects” on multinational companies’ practices abroad are assessed by comparing twelve German‐ and U.S.‐owned plants within the same sector in the “institutionally permissive” Poland, Hungary, and Slovenia. Differences are detected on functional flexibility, corporate culture and working time, but not on participation. Work organization seems more integral to national productive models than industrial relations. Moreover, considerable intramodel variation reflects product‐ and labor‐market contingencies. The results support the interpretation of national models as internally heterogeneous and dynamic.
Does Acquisitive Self‐Presentation in Personality Self‐Ratings Enhance Validity? Evidence from two experimental field studies
Authors: Blickle Gerhard , Momm Tassilo , Schneider Paula B. , Gansen Dominic , Kramer Jochen
Published: May 2009

The aim of the present research was to demonstrate that acquisitive self‐presentation in personality scales is not a barrier to their criterion‐related validities in human resource contexts, but rather a means to improve them. A pilot study (Study 1) with 96 job incumbents provided preliminary positive evidence. In Study 2, in the experimental group (n=99), the instructions asked job incumbents to work on a Big‐Five personality inventory (BFI‐K) as if they took part in a personnel selection procedure for a personally very attractive position. In the control group (n=93) of Study 2, job incumbents were asked to answer the inventory items honestly. As expected, the correlation between the self‐ratings of the motive to get along (i.e., which comprises emotional stability, conscientiousness, and agreeableness) and contextual performance assessments was significantly higher in the experimental group than in the control group in Study 2. Additionally, the correlation between the self‐ratings of the motive to get ahead (i.e., which comprises extraversion and openness to experience) and task performance and leadership assessments was significantly higher in the experimental group than in the control group in Study 2. It is proposed that responding to a personality inventory in a human resource decision situation should be conceptualized as a workplace simulation.
Counterproductive Work Behavior Among White‐Collar Employees: A study from Turkey
Authors: Bayram Nuran , Gursakal Necmi , Bilgel Nazan
Published: May 2009

The current study was designed to evaluate the magnitude and types of counterproductive work behaviors (CWBs) among a group of white‐collar employees from different firms. A total of 766 employees voluntarily participated in our study. We focused especially on employees' perceptions of their work environment and on their affective responses to those perceptions. Data were dependent on self‐reporting and privacy, and anonymity measures were taken into account. The five different instruments used to evaluate job satisfaction were, organizational constraints, interpersonal conflict, quantitative workload and CWB. We found a high degree of job satisfaction, a minimal quantitative workload and a limited exhibition of CWBs among our sample. Organizational constraints were found to be the most strongly correlated to exhibited CWBs, followed by interpersonal conflict and quantitative workload. Job satisfaction had a diminishing effect on CWBs. Among the five dimensions of CWBs, abuse and withdrawal were found to be the most important. The most frequently reported CWB was ‘came to work late without permission.’ Except for income we found no statistically significant relationship between demographic characteristics and the exhibition of CWBs. We concluded that by abolishing pre‐existing organizational constraints there may be a reduction in CWBs.
Predicting Military Performance from Specific Personality Measures: A validity study
Authors: Bilgiç Reyhan , Sümer H. Canan
Published: May 2009

This study examined the criterion‐related validity of the dimensions of a customized personality inventory in predicting different aspects of military performance. A cross‐validity study was also carried out to establish the stability of the obtained regression weights. The sample consisted of 733 non‐commissioned officers who filled out the personality inventory. Three different measures of performance (i.e., commendations, reprimands, and cumulative ranking) were used as the criteria in validating the inventory. Among the 11 dimensions of the inventory, emotional stability, directing and monitoring, self‐discipline, and military bearing predicted commendations; determination was the only predictor for reprimands, and cumulative ranking was predicted by determination and adaptability. The cross‐validity procedure showed that the obtained regression weights were stable, providing further support for the validity of the personality measures. Results yielded support for the argument that specific personality measures could be respectable predictors of different aspects of military performance.
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.
Urethral injury associated with minimally invasive mid‐urethral sling procedures for the treatment of stress urinary incontinence: a case series and systematic literature search
Authors: Morton HC , Hilton P
Published: May 2009

The introduction of the TVT™ has brought about dramatic changes in our practice as regards surgery for stress urinary incontinence, although the risk of bladder injury has caused concern. The subsequent development of tapes introduced through the obturator foramina may limit the rate of bladder injury, and some have suggested that cystoscopy is no longer required during stress incontinence surgery. Several cases of urethral injury referred to our unit have caused us concern about this approach. We present here brief details of these cases along with a systematic search of the literature on urethral injury following mid‐urethral tape procedures.
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

Antipsychotics 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

Over 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.
Preventive and therapeutic anti‐inflammatory properties of the sesquiterpene α‐humulene in experimental airways allergic inflammation
Authors: Rogerio Alexandre P. , Andrade Edinéia L. , Leite Daniela F.P. , Figueiredo Cláudia P. , Calixto João B.
Published: May 2009

Background and purpose: α‐Humulene andtrans‐caryophyllene are plant sesquiterpenes with pronounced anti‐inflammatory properties. Here, we evaluated the effects of these compounds in an experimental model of airways allergic inflammation.

Experimental approach: Female BALB/c mice, sensitized to and challenged with ovalbumin received daily α‐humulene ortrans‐caryophyllene (50 mg·kg−1, orally) or α‐humulene (1 mg·mL−1, by aerosol) as either a preventive (for 22 days) or therapeutic (from the 18th to the 22nd day) treatment. Dexamethasone or budesonide was used as a positive control drug. Inflammation was determined on day 22 post‐immunization by leukocyte recruitment, interleukin‐5 (IL‐5), CCL11, interferon‐γ (IFN‐γ) and leukotriene (LT)B4levels in bronchoalveolar lavage fluid (BALF). In addition, transcription factors [nuclear factor κB (NF‐κB), activator protein 1 (AP‐1)] and P‐selectin in lung tissue were measured by immunohistochemistry and mucus secretion by histochemistry.

Key results: Preventive or therapeutic treatments with α‐humulene, but not withtrans‐caryophyllene, significantly reduced the eosinophil recruitment to the BALF. In addition, α‐humulene recovery INF‐γ and reduced the IL‐5, CCL11 and LTB4levels in BALF, as well as the IL‐5 production in mediastinal lymph nodes (in vitroassay). Furthermore, α‐humulene decreased the NF‐kB and the AP‐1 activation, the expression of P‐selectin and the increased mucus secretion in the lung.

Conclusions and implications: α‐Humulene, given either orally or by aerosol, exhibited marked anti‐inflammatory properties in a murine model of airways allergic inflammation, an effect that seemed to be mediated via reduction of inflammatory mediators, adhesion molecule expression and transcription factors activation.

This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visithttp://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
The influence of age on the distribution of morphine and morphine‐3‐glucuronide across the blood–brain barrier in sheep
Authors: Bengtsson J , Ederoth P , Ley D , Hansson S , Amer‐Wåhlin I , Hellström‐Westas L , Marsál K , Nordström C‐H , Hammarlund‐Udenaes M
Published: May 2009

Background and purpose: The effect of age on the distribution of morphine and morphine‐3‐glucuronide (M3G) across the blood–brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied.

Experimental approach: Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg·kg−1, was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography‐tandem mass spectrometry. The half‐life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (Kp,uu) and unbound drug volume of distribution in brain (Vu,brain) were estimated.

Key results: Morphine Kp,uuwas 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine Vu,brainmeasurements were higher in sheep than in premature lambs. The M3G Kp,uuvalues were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups.

Conclusions and implications: The morphine Kp,uuwas above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.
Clinical Significance of IgG Antibody Titer against Helicobacter pylori
Authors: Tatemichi Masayuki , Sasazuki Shizuka , Inoue Manami , Tsugane Shoichiro ,   for the JPHC Study Group
Published: May 2009

Background: We clarified the clinical significance of measurement of IgG antibody titers against Helicobacter pylori using data from a nested case–control study from a large‐scale cohort study in Japan.

Method: Participants included 36,745 subjects from the Japan Health Center‐based Prospective Study who responded to the baseline questionnaire and provided a blood sample. Subjects were aged 40–69 years and were followed over 15 years after initial sampling. Controls were matched to 511 gastric cancer patients. Plasma surface antigen (Hp)‐IgG titer was measured using ELISA, and mucosal atrophy was determined by measuring pepsinogen I and II levels.

Results: Seropositive subjects with low Hp‐IgG titer and mucosal atrophy showed a higher risk for gastric cancer than high‐titer subjects. Odds ratio (OR) referred to cases with true negative IgG titers and no mucosal atrophy. In moderately atrophic subjects, the low titer OR was 19.0, with a 95% confidence interval (CI) of 7.7–46.9, and 12.5 for high titer, with a 95% CI of 5.2–30.0. In severely atrophic subjects, the low titer OR was almost double that of high‐titer subjects (OR = 30.2, 95% CI = 12.4–73.7 and OR = 15.9, 95% CI = 6.3–40.3, respectively). These associations were observed more frequently for differentiated than undifferentiated gastric cancer.

Conclusion: Combination assay with Hp‐IgG titer and pepsinogens may help identify groups at high risk for gastric cancer. Subjects with low Hp‐IgG titer and mucosal atrophy were at extremely high risk for gastric cancer, particularly differentiated cancer. Subjects with this background may require ongoing observation and periodic endoscopic examination for early cancer detection.
Single‐pulse electrical stimulation helps to identify epileptogenic cortex in children
Authors: Flanagan Danny , Valentín Antonio , García Seoane Jorge J. , Alarcón Gonzalo , Boyd Stewart G.
Published: May 2009

Purpose:  The usefulness of single‐pulse electrical stimulation (SPES) during intracranial recordings was evaluated in a pediatric population. This method is useful in identifying epileptogenic cortex in adult subjects.

Methods:  We studied 35 children who were undergoing intracranial electroencephalography (EEG) recordings from two hospitals (King’s College Hospital and Great Ormond Street Hospital for Sick Children, London, United Kingdom). In each patient we studied all available contacts using a series of 10 or more single, brief (1 ms) electrical stimuli. The cortical responses were reviewed in detail. The data were examined for associations between response type, ictal onset zone, lesion boundary, and seizure outcome.

Results:  We identified cortical responses to SPES that were similar to those reported in adults. In agreement with previous studies we found that two types of responses (“delayed” and “repetitive” responses) were associated with the ictal onset zone and the area of the presumed epileptogenic lesion. When these responses were present (54% of cases), the removal of the entire area responsible for the abnormal responses to SPES was associated with good outcome.

Conclusion:  Cortical responses to SPES in children provide new and additional information in the investigation of epileptogenic cortex in children during assessment for epilepsy surgery. This may improve the outcome for this difficult but important group.
Multidrug‐resistant genotype (ABCB1) and seizure recurrence in newly treated epilepsy: Data from international pharmacogenetic cohorts
Authors: Szoeke Cassandra , Sills Graeme J. , Kwan Patrick , Petrovski Slave , Newton Mark , Hitiris Nikolas , Baum Larry , Berkovic Samuel F. , Brodie Martin J. , Sheffield Leslie J. , O’Brien Terence J.
Published: May 2009

Purpose:  The association between a specific polymorphism (3435C>T) in the ABCB1 gene, coding for the membrane drug transporter P‐glycoprotein (PgP), and pharmacoresistance to seizure control is controversial. Studies have been limited by multiple drug use, chronic cohorts with varying definitions, and retrospective clinical data. Herein we examine the relationship of this polymorphism with seizure recurrence in three independent international cohorts of patients newly treated for epilepsy.

Methods:  Data were collected on demographics, medication details, and seizure control after 12 months of treatment. The distribution of ABCB1 3435C>T genotypes was compared between patients with and without recurrent unprovoked seizures.

Results:  Five hundred forty‐two newly treated patients were enrolled (212 from Australia, 285 from Scotland, and 45 from Hong Kong). A total of 38.4% had recurrent unprovoked seizures after starting antiepileptic drug (AED) treatment. Genotype frequencies and ethnicity did not differ between the Scottish and Australian cohorts, but both were significantly different in the Hong Kong cohort. There was no significant relationship between the ABCB1 3435C>T genotype and the rate of recurrence of unprovoked seizures in the three cohorts individually or combined; however the epilepsy syndrome and a greater number of seizures pretreatment was associated with an increased risk of seizure recurrence.

Conclusions:  The ABCB1 3435C>T genotype does not have a major role in determining the efficacy of seizure control with initial AED therapy. The study highlights issues that arise in combining pharmacogenetic datasets from different ethnic regions and health systems, an approach that is essential to advance this field.
Kv4.2 knockout mice demonstrate increased susceptibility to convulsant stimulation
Authors: Barnwell L. Forbes S. , Lugo Joaquin N. , Lee Wai L. , Willis Sarah E. , Gertz Shira J. , Hrachovy Richard A. , Anderson Anne E.
Published: May 2009

Purpose:  Kv4.2 subunits contribute to the pore‐forming region of channels that express a transient, A‐type K+ current (A‐current) in hippocampal CA1 pyramidal cell dendrites. Here, the A‐current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A‐current in area CA1 dendrites, producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro.

Methods:  Electroencephalogram electrode‐implanted Kv4.2 knockout and wild‐type mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wild‐type mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wild‐type mice following the bath application of bicuculline.

Results:  No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wild‐type littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wild‐type littermates.

Discussion:  These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold.
Probiotic‐associated high‐titer anti‐B in a group A platelet donor as a cause of severe hemolytic transfusion reactions
Authors: Daniel‐Johnson Jennifer , Leitman Susan , Klein Harvey , Alter Harvey , Lee‐Stroka Agnes , Scheinberg Phillip , Pantin Jeremy , Quillen Karen
Published: May 2009

BACKGROUND: Hemolytic transfusion reactions (HTRs) can occur with transfusion of platelets (PLTs) containing ABO‐incompatible plasma. Reported cases have involved group O donors. Two cases of PLT‐mediated HTRs associated with the same group A plateletpheresis component, collected from a donor taking high doses of probiotics are reported.

CASE REPORT: Case 1 was a 40‐year‐old 69‐kg group B stem cell transplant patient who received one‐half of a group A plateletpheresis component. Severe back pain occurred 10 minutes into the transfusion, accompanied by anemia and hyperbilirubinemia. Case 2 was a 5‐year‐old 26‐kg group B male with aplastic anemia who received the other half of the same plateletpheresis component, volume reduced to 37 mL. Syncope occurred immediately after the transfusion, with laboratory evidence of hemolysis a few hours later.

RESULTS: Serologic investigation of posttransfusion samples from both patients revealed positive direct antiglobulin tests: C3d only for Case 1 and immunoglobulin (Ig)G and C3d for Case 2; the eluates contained anti‐B. The group A donor's anti‐B titer was 16,384 at saline and IgG phases. Donor lookback revealed that the donor had donated 134 apheresis PLTs over many years. For 3 years, he had intermittently taken probiotics; 3 weeks before the index donation, he began taking three tablets of probiotics every day. Lookback of prior group B recipients uncovered a case of acute hemolysis that was not recognized at the time. The solubilized probiotic inhibited anti‐B in vitro.

CONCLUSION: Non–group O PLT donors can have high‐titer anti‐A or anti‐B that might mediate HTRs, and probiotic ingestion in blood donors represents a novel mechanism of stimulating high‐titer anti‐B.
Usefulness of Multichannel Holter ECG Recording in the Third Intercostal Space for Detecting Type 1 Brugada ECG: Comparison with Repeated 12‐Lead ECGs
Authors: SHIMENO KENJI , TAKAGI MASAHIKO , MAEDA KEIKO , TATSUMI HIROAKI , DOI ATSUSHI , YOSHIYAMA MINORU
Published: May 2009

Introduction: Type 1 Brugada ECG is essential for the diagnosis of Brugada syndrome. We aimed to evaluate the usefulness of multichannel Holter ECG recording in the third intercostal space for detecting type 1 Brugada ECG.

Methods and Results: We enrolled 60 consecutive individuals with type 1 Brugada ECG and 31 individuals with type 2 or 3 Brugada ECG, in the presence or absence of Na+ channel blockers. All individuals underwent 12‐lead ECGs recorded in the standard position and the third intercostal space at least 5 times every 3 months (4L‐ECGs, 3L‐ECGs, respectively) and multichannel Holter ECG. On multichannel Holter ECG, the precordial electrodes were attached at standard positions (4L‐Holter) and the third intercostal space (3L‐Holter) for leads V1 and V2. Among the 60 individuals, type 1 Brugada ECG in 4L‐ECGs, 3L‐ECGs, 4L‐Holter, and 3L‐Holter was detected in 15 (25%), 26 (43.3%), 23 (38.3%), and 33 individuals (55%), respectively, whereas detected in none of the 31 individuals. The documented duration of type 1 Brugada ECG on 3L‐Holter was significantly longer than that on 4L‐Holter (700 ± 467 vs 372 ± 422 min; P = 0.01, 3L‐Holter vs 4L‐Holter, respectively), and type 1 Brugada ECG was most frequently observed between 6 pm and 12 pm. Neither the presence nor the duration of the appearance of type 1 Brugada ECG differed significantly between symptomatic and asymptomatic individuals.

Conclusion: Multichannel Holter ECG recording in the third intercostal space is more sensitive and useful for the diagnosis of type 1 Brugada ECG than repeated 12‐lead ECGs or multichannel Holter ECG in the standard position.
Lifecourse Priorities Among Appalachian Emerging Adults: Revisiting Wallace's Organization of Diversity
Authors: Brown Ryan A. , Rehkopf David H. , Copeland William E. , Costello E. Jane , Worthman Carol M.
Published: May 2009

Abstract
We examine how social demographics (gender, age, or race–ethnicity), census tract characteristics, and family environment during childhood relate to variability in the lifecourse priorities of 344 Cherokee and white youth during emerging adulthood (age 19–24). Analyses were performed using recursive partitioning and random forest methods to examine determinants of prioritizing education, family formation, economic establishment, self characteristics and close relationships, youth independence, conspicuous consumption, and community reliance. Overall, characteristics of census tracts were the most common and influential predictors of lifecourse priorities. Childhood family poverty, parental relationship problems, parental crime, and stressful life events were also important predictors. Race–ethnicity or cultural group (Cherokee vs. white), age, and gender were relatively unimportant. At this developmental stage and in this population, community characteristics and childhood family experiences may be better proxies for developmental settings (and resulting enculturated values and preferences) than social demographic variables (e.g., ethnicity or gender). [lifecourse, emerging adulthood, recursive partitioning, American Indian, Appalachia]