bluuebunny/crossref_metadata_2025 huggingface dataset:
The contribution of the endogenous TRPV1 ligands 9‐HODE and 13‐HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms
Authors: Alsalem Mohammad , Wong Amy , Millns Paul , Arya Pallavi Huma , Chan Michael Siang Liang , Bennett Andrew , Barrett David A , Chapman Victoria , Kendall David A
Published: December 2012

Background and Purpose

The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9‐ and 13‐ hydroxyoctadecadienoic acid (HODE)] to TRPV1‐mediated noxious responses and inflammatory pain responses.

Experimental Approach

9‐ and 13‐HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan‐inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9‐HODE‐ and 13‐HODE‐evoked responses, and the contribution of 15‐lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9‐ and 13‐HODE and 15‐lipoxygenase to inflammatory pain behaviour.

Key Results

9‐HODE (35 ± 7 pmol g−1) and 13‐HODE (32 ± 6 pmol g−1) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9‐ and 13‐HODE were detected in DRGs and TRPV1 antagonist‐sensitive calcium responses evoked, which were blocked by the 15‐lipoxygenase inhibitor PD146176 and an anti‐13‐HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan‐inflamed hindpaw (P < 0.05), whereas levels of 9‐ and 13‐HODE were, however, decreased. Intraplantar co‐administration of anti‐9‐ and 13‐HODE antibodies and treatment with PD146176 significantly (P < 0.01) attenuated carrageenan‐induced hyperalgesia.

Conclusions and Implications

This study demonstrates that, although 9‐ and 13‐HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal.
The sensory dorsal organs of crustaceans
Authors: Lerosey‐Aubril Rudy , Meyer Roland
Published: December 2012

The cuticle of crustaceans bears numerous organs, of which the functions of many are unknown. One of these, the sensory dorsal organ (SDO), is present in a wide diversity of taxa. Here we critically review the variability, ultrastructure, distribution, and possible function of this enigmatic cuticular organ. Previous data are complemented by new observations on larvae and adults of various malacostracans. The SDO is composed of four sensors arranged as the corners of a square, the centre of which is occupied by a gland. Pores or pegs surrounding this central complex may also form part of the organ. The arrangement and the external aspect of the five main elements varies greatly, but this apparently has little impact on their ultrastructural organisation. The sensors and the gland are associated with a particularly thin cuticle. Each sensor contains four outer dendritic segments and the central gland is made of a single large cell. It is not yet known what this large cell secretes. The SDO is innervated from the tritocerebrum and therefore belongs to the third cephalic segment. A similar organ, here called the posterior SDO, has been repeatedly observed more posteriorly on the carapace. It resembles the SDO but has a greater number of sensors (usually six, but up to ten) apparently associated with only two outer dendritic segments. The SDO and the posterior SDO are known in the Eumalacostraca, the Hoplocarida, and the Phyllocarida. Some branchiopods also possess a ‘dorsal organ’ resembling both the SDO and the ion‐transporting organ more typical of this group. This may indicate a common origin for these two functionally distinct groups of organs. New observations on the posterior SDO support the hypothesis that the SDO and the posterior SDO are homologous to the lattice organ complexes of thecostracans. However, the relationship between the SDO and the dorsal cephalic hump of calanoid copepods remains unclear. No correlation can be demonstrated between the presence of a SDO and a particular ecological or biological trait. In fossils, the most convincing examples of SDO‐like organs are found in some Late Cambrian arthropods from the Alum Shale of southern Sweden. They suggest that related organs might have been present in non‐crustacean Cambrian arthropods. The distribution of the SDO and posterior SDO in extant and fossil crustaceans strongly suggests that these organs originated early in the history of the group, and are crucial to the functioning of these organisms. However, except for knowing that the sensors are chemoreceptors and that in a given organ a functional relationship probably exists between them and the gland, little is known about this function. The description of a SDO in freshwater carideans, which can be easily reared in a laboratory, opens the way for behavioural and physiological experiments to be undertaken that could prove crucial for the determination of this function.
Behavioural responses of wildlife to urban environments
Authors: Lowry Hélène , Lill Alan , Wong Bob B. M.
Published: December 2012

Increased urbanization represents a formidable challenge for wildlife. Nevertheless, a few species appear to thrive in the evolutionarily novel environment created by cities, demonstrating the remarkable adaptability of some animals. We argue that individuals that can adjust their behaviours to the new selection pressures presented by cities should have greater success in urban habitats. Accordingly, urban wildlife often exhibit behaviours that differ from those of their rural counterparts, from changes to food and den preferences to adjustments in the structure of their signals. Research suggests that behavioural flexibility (or phenotypic plasticity) may be an important characteristic for succeeding in urban environments. Moreover, some individuals or species might possess behavioural traits (a particular temperament) that are inherently well suited to occupying urban habitats, such as a high level of disturbance tolerance. This suggests that members of species that are less ‘plastic’ or naturally timid in temperament are likely to be disadvantaged in high‐disturbance environments and consequently may be precluded from colonizing cities and towns.
What do we really know about the signalling role of plumage colour in blue tits? A case study of impediments to progress in evolutionary biology
Authors: Parker Timothy H.
Published: December 2012

Evolutionary biologists seek to explain the origin and maintenance of phenotypes, and a substantial portion of this research is accomplished by thorough study of individual species. For instance, many researchers study individual species to understand evolution of ornamental traits which appear to be products of sexual selection. I explored our understanding of sexual ornaments in a well‐studied vertebrate species that may serve as a case study for research programs in evolutionary biology. I attempted to located all published papers examining plumage colour and variables related to sexual selection hypotheses in a common European songbird, the blue tit (Cyanistes caeruleus). Researchers have estimated over 1200 statistical relationships with plumage colour of blue tits in 52 studies. However, of the approximately 1000 main‐effect relationships from the 48 studies that are candidates for inclusion in this meta‐analysis, more than 400 were reported without details of strength and direction. Circumstantial evidence suggests that an unknown number of other estimated effects remain unpublished. Missing information is a substantial barrier to interpretation of these papers and to meta‐analytic synthesis. Examination and analysis of funnel plots indicated that unpublished effects may be a biased sample of all effects, especially for comparisons of plumage colour to age and individual quality, and possibly also to measures of mate choice. Further, type I error was likely elevated by the large number of statistical comparisons evaluated, the frequent use of iterative model‐building procedures, and a willingness to interpret a wide variety of results as support for a hypothesis. Type I errors were made more problematic because blue tit plumage researchers only rarely have attempted to replicate important findings in their own work or that of others. Replication is essential to drawing robust scientific conclusions, especially in probabilistic systems with moderate to weak effects or a likelihood of bias. Last, researchers studying blue tit plumage have often developedad hocexplanations for deviations of results from their predictions. Revising hypotheses in light of data is appropriate, but these revised hypotheses were rarely tested with new data. The only highly robust conclusion supported by meta‐analysis is that male blue tits have plumage that reflects more light in the ultraviolet and yellow wavelengths than the plumage of females. Various other effects, including condition‐dependence of plumage colour expression and a tendency for females to adjust the sex ratio of their offspring in response to male colour, remain uncertain. These obstacles to progress in the blue tit plumage literature are likely common in evolutionary biology, and so I recommend changes to incentive structures which may improve progress towards scientific understanding in this discipline.
Factors related to advanced stages of change in a clinical sample of adolescents
Authors: Taylor Andrew , Zaitsoff Shannon L. , Paterson Ashley
Published: December 2012

Background

The purpose of the present study was to examine the factors predicting a greater motivation to change in a clinical sample of adolescents.

Method

A total of 107 adolescents participated in this research prior to beginning outpatient treatment. Participants completed a modified version of the Motivational Stages of Change for Adolescents Recovering from an ED, the Difficulties in Emotional Regulation Scale and the Behavioral Assessment System for Children–Self‐Report.

Results

More advanced stages of change were associated with better parent–adolescent relationships and better emotional regulation.

Conclusion

Incorporating parents in treatment to enhance parent–adolescent relationships and instructing parents in emotional regulation techniques to assist the adolescent may enhance their motivation to recover.
Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk
Authors: Barbieri R. B. , Bufalo N. E. , Cunha L. L. , Assumpção L. V. M. , Maciel R. M. B. , Cerutti J. M. , Ward L. S.
Published: December 2012

Context

Different inherited profiles of genes involved in cellular mechanisms of activation and detoxification of carcinogenic products can provide specific protection or determine the risk for cancer. Low‐penetrance polymorphic genes related to the biotransformation of environmental toxins have been associated with susceptibility to and the phenotype of, human tumours.

Objective

To investigate the role of germline inheritance of polymorphisms in CYP1A2*F, CYP1A1 m1, GSTP1, NAT2 and TP53 genes in hereditary medullary thyroid carcinoma (HMTC) patients.

Design

This study was developed in University of Campinas (Unicamp).

Patients

We studied 132 patients with HMTC, 88 first‐degree relatives of HMTC patients and 575 control individuals.

Measurements

All patients with MTC and their relatives were sequenced for the RET gene and five genes were genotyped using TaqMan® system.

Results

We observed that the inheritance of CYP1A2*F (OR = 2·10; 95% CI = 1·11–3·97; P = 0·022), GSTP1 (OR = 4·41; 95% CI = 2·47–7·88; P < 0·001) and NAT2 (OR = 2·54; 95% CI = 1·16–5·58; P = 0·020) variants increased the risk for HMTC. In addition, multiple regression analysis showed that the inheritance of GSTP1 polymorphisms was associated with the diagnosis in older patients (B = 8·0229; 95% IC = ± 5·5735; P = 0·0054). Concerning the group of HTMC relatives, CYP1A2*F (OR = 2:40; 95% CI = 1·19–4·86; P = 0·015), CYP1A1 m1 (OR = 2·79; 95% CI = 1:04–7·51; P = 0·042), GSTP1 (OR = 2·86; 95% IC = 1·53–5·32; P < 0·001) and NAT2 (OR = 2·25; 95% IC = 1·20–4·22; P = 0·012) were associated with HMTC risk.

Conclusions

We have demonstrated that the inheritance of specific genes determining the individual response to environmental toxins may contribute to the risk and phenotypic variability that exists in patients with HMTC. Moreover, we identified a group at risk in relatives of HMTC patients.
Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population
Authors: Jung C. H. , Lee W. J. , Hwang J. Y. , Yu J. H. , Shin M. S. , Lee M. J. , Jang J. E. , Leem J. , Park J.‐Y. , Kim H.‐K.
Published: December 2012

Aims

Fatty liver disease, especially non‐alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance.

Methods

We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow‐up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ‐glutamyltransferase, waist circumference and BMI.

Results

During a 4‐year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index‐positive) than in the group with a fatty liver index < 20 (fatty liver index‐negative) after adjusting for various confounding variables including homeostasis model assessment of insulin resistance. Odds ratios were significant regardless of the insulin resistance status at baseline.

Conclusions

Our results suggest that fatty liver index as a simple surrogate indicator of hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance.
Barriers to self‐management of diabetes
Authors: Ahola A. J. , Groop P.‐H.
Published: December 2012

People with diabetes hold major responsibility for the day‐to‐day management of their chronic condition. The management that, amongst others, includes blood glucose monitoring, medication taking, diet and physical activity, aims at normalizing blood glucose levels. In many individuals, the level of glycaemia, however, frequently exceeds the recommendations. This observation, together with patients' and practitioners' reports, suggests that active self‐management is suboptimal. Various reasons, both individual and environment related, contribute to the suboptimal concordance with treatment regimen. The aim of this review is to discuss some of the barriers to optimal diabetes self‐management.
Retracted: Effects of fasting blood glucose, diabetes treatment, blood pressure and anti‐hypertension treatment on cardiovascular disease incidence: a 30‐year follow‐up study of 740 incident patients with Type 2 diabetes
Authors: Jansson S. P. O. , Andersson D. K. G. , Svärdsudd K.
Published: December 2012

Aims

To analyse the effects of hyperglycaemia and blood pressure, diabetes and anti‐hypertension treatment on total and various types of cardiovascular disease incidence in patients with Type 2 diabetes followed for 30 years.

Methods

A total of 740 incident patients with Type 2 diabetes were registered at the Laxå Primary Health Care Centre, Sweden between 1972 and 2001. Information on systolic, diastolic, and mean arterial blood pressure, mean fasting blood glucose, type of diabetes and anti‐hypertension treatment was obtained from the patient records, and information on cardiovascular disease, myocardial infarction and stroke events from National Registers.

Results

During the follow‐up period the cumulative incidence of cardiovascular disease increased significantly with male sex (HR 1.52, 95% CI 1.25–1.85), age (HR 1.05, 95% CI 1.04–1.07), year of diabetes onset (HR 1.03, 95% CI 1.01–1.05), BMI, (HR 1.04, 95% CI 1.02–1.07), mean arterial blood pressure (HR 1.04, 95% CI 1.02–1.05) and number of previous cardiovascular disease events (HR 1.15, 95% CI 1.10–1.21), and decreased significantly with sulfonylurea treatment (HR 0.64, 95% CI 0.49–0.84), insulin (HR 0.57, 95% CI 0.33–0.98) and calcium channel blocker treatment (HR, 0.69, 95% CI 0.48–0.99). Cumulative incidence of myocardial infarction increased significantly with male sex, age, BMI, mean arterial blood pressure, number of previous myocardial infarction events and diuretic treatment, and decreased with metformin treatment. Cumulative incidence of stroke increased with age, year of diabetes onset, mean arterial blood pressure, and previous number of stroke events.

Conclusions

Cumulative cardiovascular disease, myocardial infarction and incidence of stroke increased with number of previous events and presence of hypertension and decreased with pharmacological anti‐diabetic treatment and, to a lesser extent, with anti‐hypertension treatment.
The clinical significance of overt diabetes in pregnancy
Authors: Wong T. , Ross G. P. , Jalaludin B. B. , Flack J. R.
Published: December 2012

Aim

To explore clinical implications of overt diabetes in pregnancy on antenatal characteristics, adverse neonatal outcome and diabetes risk post‐partum.

Methods

Retrospective audit of prospectively collected data for all patients with gestational diabetes mellitus from 1993 to 2010. We defined overt diabetes in pregnancy as an HbA1c ≥ 8 mmol/mol (6.5%) or a fasting plasma glucose ≥ 7.0 mmol/l, or a 2‐h glucose level ≥ 11.1 mmo/L on a 75‐g oral glucose tolerance test as a surrogate for a random glucose ≥ 11.1 mmo/l.

Results

Our audit identified 1579 women with gestational diabetes and 254 with overt diabetes in pregnancy. Women with overt diabetes in pregnancy were diagnosed earlier in pregnancy, had a higher number of risk factors for gestational diabetes, higher antenatal HbA1c, fasting and 2‐h glucose levels, higher pre‐pregnancy BMI and higher insulin use and dosage requirements than those with gestational diabetes. Overt diabetes in pregnancy was associated with an increased rate of large‐for‐gestational‐age infant, neonatal hypoglycaemia and shoulder dystocia. Of the 133 patients with overt diabetes in pregnancy who attended a follow‐up oral glucose tolerance test at 6–8 weeks post‐partum, 21% had diabetes, 37.6% had impaired fasting glucose or impaired glucose tolerance, whilst 41.4% returned to normal glucose tolerance.

Conclusion

In this patient cohort, overt diabetes in pregnancy significantly increased the risk of adverse pregnancy outcomes and post‐partum impaired glucose regulation, but should not be regarded as synonymous with underlying diabetes. Two‐hour glucose following a 75‐g glucose load is a poor predictor of post‐partum diabetes.
Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance
Authors: Putz Z. , Németh N. , Istenes I. , Martos T. , Gandhi R. A. , Körei A. E. , Hermányi Z. , Szathmári M. , Jermendy G. , Tesfaye S. , Tabák Á. G. , Kempler P.
Published: December 2012

Aims

To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population.

Methods

Seventy‐five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10‐year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24‐h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure – mean night‐time blood pressure) × 100/mean daytime blood pressure.

Results

Mean 24‐h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± sd) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non‐dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results.

Conclusion

Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.
Reversal of ophthalmic artery flow as a predictor of intracranial hemodynamic compromise: implication for prognosis of severe carotid stenosis
Authors: Tsai C.‐L. , Lee J.‐T. , Cheng C.‐A. , Liu M.‐T. , Chen C.‐Y. , Hu H.‐H. , Peng G.‐S.
Published: December 2012

Background and purpose

High‐grade cervical carotid stenosis (70–99%) or occlusion often accompanies reversed ophthalmic artery flow (ROAF), but its potential clinical significances remain poor understood. This study assessed ROAF and the related variables caused by carotid hemodynamic compromise in patients with unilateral severe cervical carotid stenosis.

Methods

The study consisted of 200 patients diagnosed as unilateral high‐grade cervical carotid stenosis/occlusion using ultrasonography. The hemodynamic parameters of 152 patients, excluding 48 with cervical carotid occlusion, were compared based on the presence of ROAF. Out of 200 patients, 159 underwent brain magnetic resonance imaging and were analysed for risk factors impacting functional outcomes including ROAF.

Results

The patients (n = 48) with internal carotid artery occlusion had significantly higher incidence (62.5%) of ROAF compared with that of 25.0% in those patients (n = 152) with unilateral high‐grade carotid stenosis (P < 0.001). In ROAF patients (n = 38) with the unilateral high‐grade stenosis, a significant retrobulbar arteries hemodynamic difference was observed between the stenotic and non‐stenotic vessels. The patients (n = 159) with history of stroke (P = 0.035), ROAF (P = 0.023) and intracranial stenosis (P < 0.001) exhibited significantly higher incidence of poor functional outcome compared with the corresponding control groups. In the same patients (n = 159), those with both cervical and intracranial stenosis showed sevenfold higher risk (OR, 7.60; 95% CI, 3.44–16.81) for ROAF than those with only cervical stenosis.

Conclusions

ROAF may result from intracranial hemodynamic compromise. Patients with unilateral high‐grade cervical carotid stenosis/occlusion in combination with intracranial stenosis appear to be a significant risk factor for poor functional outcome and increased incidence of ROAF.
Recognition of facial and musical emotions in Parkinson's disease
Authors: Saenz A. , Doé de Maindreville A. , Henry A. , de Labbey S. , Bakchine S. , Ehrlé N.
Published: December 2012

Background and purpose

Patients with amygdala lesions were found to be impaired in recognizing the fear emotion both from face and from music. In patients with Parkinson's disease (PD), impairment in recognition of emotions from facial expressions was reported for disgust, fear, sadness and anger, but no studies had yet investigated this population for the recognition of emotions from both face and music.

Methods

The ability to recognize basic universal emotions (fear, happiness and sadness) from both face and music was investigated in 24 medicated patients with PD and 24 healthy controls. The patient group was tested for language (verbal fluency tasks), memory (digit and spatial span), executive functions (Similarities and Picture Completion subtests of the WAIS III, Brixton and Stroop tests), visual attention (Bells test), and fulfilled self‐assessment tests for anxiety and depression.

Results

Results showed that the PD group was significantly impaired for recognition of both fear and sadness emotions from facial expressions, whereas their performance in recognition of emotions from musical excerpts was not different from that of the control group. The scores of fear and sadness recognition from faces were neither correlated to scores in tests for executive and cognitive functions, nor to scores in self‐assessment scales.

Conclusion

We attributed the observed dissociation to the modality (visual vs. auditory) of presentation and to the ecological value of the musical stimuli that we used. We discuss the relevance of our findings for the care of patients with PD.
Prevalence of multiple sclerosis in Verona, Italy: an epidemiological and genetic study
Authors: Gajofatto A. , Stefani A. , Turatti M. , Bianchi M. R. , Lira M. G. , Moretto G. , Salviati A. , Benedetti M. D.
Published: December 2012

Background and purpose

Recent multiple sclerosis (MS) prevalence studies classify Italy as a high‐risk area without intra‐regional latitude effect.

Objectives

To determine MS prevalence in Verona, Italy, and frequency of myelin oligodendrocyte glycoprotein (MOG) gene G511C polymorphism and HLA‐DRB1*15 locus in a sample of cases and healthy controls.

Methods

The study area population on the prevalence date (31 December 2001) was 253 208 (133 508 women, 119 700 men). Multiple case sources were examined. Patients fulfilling McDonald's criteria (2001) were included. Crude, age‐ and sex‐specific prevalence rates were computed. MOG G511C polymorphism and HLA‐DRB1*15 were determined by standard methods.

Results

We identified 270 cases of MS yielding a crude prevalence rate of 106.6/100 000 (95% CI: 94–120). Prevalence was higher in women (140.8/100 000) than in men (68.5/100 000). The age‐adjusted prevalence rate standardized to the European population was 96.0/100 000. MOG G511C polymorphism did not differ between cases and controls. HLA‐DRB1*15 frequency was 58/155 (37%) in cases and 24/157 (15%) in controls (P < 0.001). There was no HLA‐DRB1*15 influence on susceptibility to other autoimmune disorders.

Conclusions

The high MS prevalence in Verona confirms Italy as a high‐risk area with a homogenous distribution across the country. HLA‐DRB1*15 is a relevant MS susceptibility locus in the Italian population, possibly with little influence on the occurrence of concomitant autoimmune disorders.
Interictal and periictal headache in patients with epilepsy: migraine‐triggered seizures or epilepsy‐triggered headache?
Authors: Belcastro V. , Striano P. , Parisi P.
Published: December 2012

Clickhereto view the accompanying paper in this issue.
Somatosensory temporal discrimination threshold may help to differentiate patients with multiple system atrophy from patients with Parkinson's disease
Authors: Rocchi L. , Conte A. , Nardella A. , Li Voti P. , Di Biasio F. , Leodori G. , Fabbrini G. , Berardelli A.
Published: December 2012

Background and purpose

Somatosensory temporal discrimination threshold (STDT) is defined as the threshold at which two tactile stimuli applied to the skin are perceived as clearly distinct.

The aim of the study was to investigate whether the extent of STDT alterations differs between patients with parkinsonian type multiple system atrophy (MSA‐P) and patients with Parkinson's disease (PD). Possible differences between the two groups may help to differentiate MSA‐P from PD.

Methods

STDT was investigated in 20 patients with MSA‐P, 21 patients with PD and 18 age‐matched healthy subjects. The clinical evaluation included the Mini‐Mental State Examination, Hoehn and Yahr Scale, Frontal Assessment Battery, Unified Multiple System Atrophy Rating Scale for patients with MSA‐P, and Unified Parkinson's Disease Rating Scale for patients with PD. STDT was investigated by delivering paired electrical stimuli starting with an inter‐stimulus interval (ISI) of 0 ms (simultaneous pair), and progressively increasing the ISIs in 10‐ms steps.

Results

Between‐group anova showed that STDT statistically differed in MSA‐P versus patients with PD and healthy subjects. Post hoc showed that STDT values in patients with MSA‐P were significantly higher than those in patients with PD and healthy subjects. Receiver operating characteristic curve analysis showed that STDT testing yielded high diagnostic specificity and sensitivity.

Conclusions

STDT is abnormal in patients with MSA‐P and PD. The degree of STDT abnormalities is higher in patients with MSA‐P than in patients with PD.
Prestroke antiplatelet therapy and early prognosis in stroke patients: the Dijon Stroke Registry
Authors: Béjot Y. , Aboa‐Eboulé C. , de Maistre E. , Jacquin A. , Troisgros O. , Hervieu M. , Osseby G. V. , Rouaud O. , Giroud M.
Published: December 2012

Background and purpose

Previous antiplatelet therapy (APT) in cardiovascular prevention is common in patients with first‐ever stroke. We aimed to evaluate the prognostic value of APT on early outcome in stroke patients.

Methods

All first‐ever strokes from 1985 to 2011 were identified from the population‐based Stroke Registry of Dijon, France. Demographic features, risk factors, prestroke treatments and clinical information were recorded. Multivariate analyses were performed to evaluate the associations between pre‐admission APT and both severe handicap at discharge, and mortality at 1 month and 1 year.

Results

Among the 4275 patients, 870 (20.4%) were previously treated with APT. Severe handicap at discharge was noted in 233 (26.8%) APT users and in 974 (28.7%) non‐users. Prestroke APT use was associated with lower odds of severe handicap at discharge [adjusted odds ratio (OR): 0.79; 95% confidence interval (CI): 063–1.00; P = 0.046], non‐significant better survival at 1 month [adjusted hazard ratio (HR): 0.87; 95% CI: 0.70–1.09; P = 0.222] and no effect on 1‐year mortality (HR: 0.94; 95% CI 0.80–1.10; P = 0.429). In stratum‐specific analyses, APT was associated with a lower risk of 1‐month mortality in patients with cardioembolic ischaemic stroke (HR: 0.65; 95% CI: 0.43–0.98; P = 0.040).

Conclusions

APT before stroke was associated with less severe handicap at discharge, with no significant protective effect for mortality at 1 month except in patients with cardioembolic stroke. No protective effect of APT was observed for mortality at 1 year. Further studies are needed to understand the mechanisms underlying the distinct effects of prior APT observed across the ischaemic stroke subtypes.
Cost‐effectiveness of onabotulinumtoxinA for the treatment of wrist and hand disability due to upper‐limb post‐stroke spasticity in Scotland
Authors: Doan Q. V. , Gillard P. , Brashear A. , Halperin M. , Hayward E. , Varon S. , Lu Z. J.
Published: December 2012

Background and purpose

The objective was to evaluate the cost‐effectiveness of treating upper‐limb post‐stroke spasticity (ULPSS) with usual care (UC) plus onabotulinumtoxinA versus UC alone in Scotland.

Methods

We developed a model to simulate costs and quality‐adjusted life years (QALYs) gained from treating ULPSS. Efficacy data and health utilities were taken from clinical trials. Unit costs were taken from published Scottish sources. We compared UC plus onabotulinumtoxinA and UC alone in three scenarios: (i) a scenario from the National Health Service perspective, which included differences in onabotulinumtoxinA use, specialist visits and day‐hospital visits; (ii) a scenario that only included differences in onabotulinumtoxinA use and specialist visits; and (iii) a scenario from a societal perspective that included differences in onabotulinumtoxinA use, specialist visits and caregiver burden.

Results

In the first scenario, the model predicted that UC plus onabotulinumtoxinA produced 0.107 QALYs at an additional cost of £1099 compared with UC alone over 5 years, resulting in an incremental cost‐effectiveness ratio (ICER) of £10 271/QALY. In the second scenario, the ICER increased to £27 134/QALY. In the third scenario (societal perspective), UC plus onabotulinumtoxinA produced lower total cost and higher QALYs, and therefore was superior to UC alone.

Conclusions

Based on a model, UC plus onabotulinumtoxinA improved disability, which translated into greater QALYs but also increased direct medical costs compared with UC alone; however, the resulting ICER can be considered cost‐effective. Moreover, UC plus onabotulinumtoxinA can be cost‐saving if reduction in caregiver burden was included. OnabotulinumtoxinA offers value for money in the management of ULPSS in Scotland.
Collateral circulation on perfusion‐computed tomography‐source images predicts the response to stroke intravenous thrombolysis
Authors: Calleja A. I. , Cortijo E. , García‐Bermejo P. , Gómez R. D. , Pérez‐Fernández S. , del Monte J. M. , Muñoz M. F. , Fernández‐Herranz R. , Arenillas J. F.
Published: December 2012

Background and purpose

Perfusion‐computed tomography‐source images (PCT‐SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT‐SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis.

Methods

We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color‐coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT‐SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2–3) vs. poor (scores 0–1) collaterals. The predetermined primary end‐point was a good 3‐month functional outcome, while early neurological recovery, transcranial duplex‐assessed 24‐h MCA recanalization, 24‐h hypodensity volume and hemorrhagic transformation were considered secondary end‐points.

Results

Fifty‐four patients were included (55.5% women, median NIHSS 10), and 4‐13‐23‐14 patients had LMC score (LMCs) of 0‐1‐2‐3, respectively. The probability of a good long‐term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good‐LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23–197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate.

Conclusions

A higher degree of LMC assessed by PCT‐SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.
A Common Marking Technique Affects Tadpole Behavior and Risk of Predation
Authors: Carlson Bradley E. , Langkilde Tracy
Published: December 2012

In many studies, it is necessary for researchers to mark individual animals for later identification. It is often assumed in the interpretation of these studies that marks have no effects on the biology of the animals. This assumption is insufficiently tested, and, when it is, coarse assessments of negative effects are often used, such as survival and growth under simplified laboratory conditions. We examined the consequences of a common larval amphibian marking technique (staining with methylene blue) for wood frog tadpole behavior and survival in an ecologically realistic scenario (predation). We measured a number of tadpole behavioral variables, under baseline conditions and in the presence of olfactory cues of a predator, for marked and unmarked tadpoles. We then exposed pairs of tadpoles (one marked and one unmarked) to one of two predators and tested for the effects of marking on the susceptibility of tadpoles to predation. We found that marking suppressed the increase in movement rate that typically occurred in (unmarked) tadpoles in the presence of predator cues. Marked tadpoles were significantly more likely to be captured by predators, an effect that could not be attributed to this difference in movement rate. These results raise concern about the use of this staining method and highlight the need for studies involving marked animals to thoroughly address any relevant effects the marks may have on the biology of the subjects.
Pathological and clinical features associated with palmar/plantar osteochondral disease of the metacarpo/metatarsophalangeal joint in Thoroughbred racehorses
Authors: Pinchbeck G. L. , Clegg P. D. , Boyde A. , Riggs C. M.
Published: December 2012

Reasons for performing study

Palmar/plantar osteochondral disease (POD) of the metacarpo/metatarsophalangeal (Mc/MtPh) joints is common in Thoroughbred racehorses, but there is little information on predilection sites, associated pathologies and clinical signs.

Objectives

To describe the distribution of POD at post mortem examination and to examine the association of POD with other pathologies and clinical histories.

Methods

The Mc/MtPh joints of 102 Thoroughbred racehorses were examined post mortem. Gross pathology of associated osteochondral elements, suspensory ligament and flexor tendons was recorded. Clinical data were extracted from computerised records. Relationships between all Mc/MtPh joint pathologies, clinical data and grade of POD in each condyle were determined using multilevel, ordinal logistic regression models.

Results

Palmar/plantar osteochondral disease was recorded (grade 1–3 in at least one condyle) in 80.4% (95% confidence interval 71–88) of horses. The grade of POD was significantly higher in the forelimb, where the medial condyle had higher grades, than in the hindlimb, where the POD grade was higher in the lateral condyle. There was a significant positive relationship between POD grade and multiple other joint pathologies, whereas grades of linear fissures had a negative relationship with grade of POD. There was no relationship between grade of POD and tendon and suspensory ligament gross pathology, although horses with a history of tendon injury had significantly lower POD grades. Horses that had a clinical history of a Mc/MtPh joint problem had higher POD grades. In addition, horses that had been retired from racing for more than 2 months at the date of death had significantly lower POD grades.

Conclusions and potential relevance

Palmar/plantar osteochondral disease has specific predilection sites. Horses with a clinical history of Mc/MtPh‐associated lameness had higher POD grades, whereas those with a history of superficial digital flexor tendon injury and retired horses had lower grades. The progression of POD and its ability to heal requires further evaluation.
Ultrasound features of arytenoid chondritis in Thoroughbred horses
Authors: Garrett K. S. , Embertson R. M. , Woodie J. B. , Cheetham J.
Published: December 2012

Reasons for performing study

Laryngeal ultrasonography can provide valuable information when considering a diagnosis of arytenoid chondritis, but specific ultrasonographic parameters have not been defined.

Objectives

To compare ultrasonographic findings of the arytenoid cartilages in horses with endoscopically diagnosed arytenoid chondritis with ultrasonographic findings of the arytenoid cartilages in normal horses.

Methods

Ultrasound images of the larynx were obtained at the level of the arytenoid cartilages in horses with endoscopically diagnosed arytenoid chondritis and horses with normal arytenoid cartilage structure and function. Information obtained from the ultrasound examination included arytenoid cartilage cross‐sectional area, arytenoid cartilage echogenicity and arytenoid cartilage shape. Comparisons were performed between affected and unaffected arytenoid cartilages. For horses with multiple examinations, relationships between time point and arytenoid cartilage cross‐sectional area were determined.

Results

Chondritic arytenoid cartilages were significantly larger and had abnormal shape and echogenicity when compared with normal arytenoid cartilages (P<0.001). For horses with multiple examinations, no significant changes were identified in arytenoid cartilage size over time.

Conclusions

Chondritic arytenoid cartilages are increased in size and have abnormal echogenicity and contour in comparison with normal arytenoid cartilages when assessed using laryngeal ultrasonography. Once enlarged, the cartilage does not appear to return to normal size after the infection and/or inflammation has resolved.

Potential relevance

Ultrasonography is a valuable diagnostic modality when investigating cases of possible arytenoid chondritis or abnormal arytenoid cartilage movement. It has additional benefit in determining the extent of disease when medial masses are present on the surface of arytenoid cartilages, aiding in surgical decision making.
Horse‐, training‐ and race‐level risk factors for palmar/plantar osteochondral disease in the racing Thoroughbred
Authors: Pinchbeck G. L. , Clegg P. D. , Boyde A. , Barr E. D. , Riggs C. M.
Published: December 2012

Reasons for performing study

Palmar/plantar osteochondral disease (POD) is a common, debilitating condition in Thoroughbred racehorses; however, training‐ and racing‐related factors associated with this disease are unknown.

Objectives

To determine horse‐, racing‐ and training‐related risk factors for POD. The general hypotheses were that early training and racing, and increased intensity of racing and training, lead to increased severity of POD.

Methods

The metacarpo/metatarsophalangeal joints of 164 Thoroughbred racehorses were examined at post mortem and graded for third metacarpal and metatarsal POD. The relationships between training‐ and racing‐related factors and grade of POD in each condyle were determined using multilevel, multivariable, ordinal logistic regression models.

Results

A total of 1288 condyles were graded. Factors associated with higher grades of POD were the total lifetime number of races, an increase in gallop sessions in the previous season, racing before import to Hong Kong and an increase in the number of short (8–16 weeks) between‐race intervals per season. Horses in their first racing season were more likely to have lower POD grades, while horses that had a long between‐race interval (greater than 16 weeks) in the season prior to euthanasia were also more likely to have lower POD grades. Lower POD grades were significantly more likely as days since last race increased up to 400 days. Age at first race was not significantly associated with grade of POD.

Conclusions and potential relevance

Cumulative racing exposure and training intensity in the previous season were associated with higher grades of POD, supporting the hypothesis that the disease is due to repetitive loading. Longer between‐race intervals and increased time since racing were associated with lower POD grades, which may indicate that lesions heal. Further work is required to enable optimisation of racing and training programmes to reduce the frequency and severity of this disease.
Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma
Authors: Puig‐Butillé Joan A. , Badenas Celia , Ogbah Zighereda , Carrera Cristina , Aguilera Paula , Malvehy Josep , Puig Susana
Published: December 2012

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.
Self‐trimerization of ExsD limits inhibition of the Pseudomonas aeruginosa transcriptional activator ExsA in vitro
Authors: Bernhards Robert C. , Marsden Anne E. , Esher Shannon K. , Yahr Timothy L. , Schubot Florian D.
Published: December 2012

The opportunistic pathogen Pseudomonas aeruginosa ranks among the leading causes of nosocomial infection. The type III secretion system (T3SS) aids acute Pseudomonas aeruginosa infection by injecting potent cytotoxins into host cells to suppress the host's innate immune response. Expression of all T3SS‐related genes is strictly dependent on the transcription factor ExsA. Consequently, ExsA and the biological processes that regulate ExsA function are of great biomedical interest. The present study focused on the ExsA–ExsC–ExsD–ExsE signaling cascade, which ties host cell contact to the upregulation of T3SS gene expression. Prior to T3SS induction, the antiactivator protein ExsD binds to ExsA and blocks ExsA‐dependent transcription by interfering with ExsA dimerization and promoter interactions. Upon host cell contact, ExsD is sequestered by the T3SS chaperone ExsC, resulting in the release of ExsA and upregulation of the T3SS. Previous studies have shown that the ExsD–ExsA interactions are not freely reversible. Because independently folded ExsD and ExsA were not found to interact, it has been hypothesized that folding intermediates of the two proteins form the complex. Here, we demonstrate, for the first time, that ExsD alone is sufficient to inhibit ExsA‐dependent transcription in vitro and that no other cellular factors are required. More significantly, we show that independently folded ExsD and ExsA are capable of interacting, but only at 37 °C and not at 30 °C. Guided by the crystal structure of ExsD, we designed a monomeric variant of the protein, and demonstrated that ExsD trimerization prevents ExsD from inhibiting ExsA‐dependent transcription at 30 °C. We propose that this unique mechanism plays an important role in T3SS regulation.

Structured digital abstract

ExsD and ExsD bind by molecular sieving (View interaction).

ExsA physically interacts with ExsA by protein complementation assay (View interaction).