bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of depression risk in LGI1 mutation carriers
Authors: Heiman Gary A. , Kamberakis Kay , Gill Richard , Kalachikov Sergey , Pedley Timothy A. , Allen Hauser W. , Ottman Ruth
Published: July 2010

Purpose:  Depression is the most common comorbid condition in epilepsy. The cause of this comorbidity is unknown, and could involve psychosocial consequences of epilepsy, treatment side effects, seizure manifestations, or common neurobiologic mechanisms. One hypothesis of particular interest is a shared genetic susceptibility to epilepsy and depression. We tested this hypothesis by studying depressive symptoms in families with an identified genetic form of epilepsy: autosomal dominant partial epilepsy with auditory features caused by mutations in the leucine‐rich, glioma inactivated 1 gene (LGI1).

Methods:  A standardized depression screen was administered to 94 individuals from 11 families with mutations in LGI1, including 38 mutation carriers with epilepsy (AC), 11 clinically unaffected mutation carriers (UC), and 45 noncarriers (NC).

Results:  Current depressive symptom scores were significantly higher in AC than in NC, an association that remained after excluding depressive symptoms that appeared likely to be caused by antiepileptic medication use. However, scores did not differ between UC and NC.

Discussion:  Although LGI1 mutation carriers who were clinically affected with epilepsy had increased depressive symptoms, mutation carriers without epilepsy did not. These findings suggest that the increase in depressive symptoms in affected individuals from these families is related to epilepsy or its treatment rather than to LGI1 mutations per se.
Familial partial epilepsy with variable foci: A new family with suggestion of linkage to chromosome 22q12
Authors: Morales‐Corraliza José , Gómez‐Garre Pilar , Sanz Raúl , Díaz‐Otero Fernando , Gutiérrez‐Delicado Eva , Serratosa José M.
Published: July 2010

Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant form of partial epilepsy characterized by the presence of epileptic seizures originating from different cerebral lobes in different members of the same family. Linkage to chromosomes 22q12 and 2q36 has been reported, although only six families have been published. We studied a new FPEVF family including nine affected individuals. The phenotype in this family was similar to that previously described and consisted of nocturnal and daytime seizures with semiology suggesting a frontal lobe origin. A video‐EEG (electroencephalography) recording of the proband’s seizures is presented and revealed hyperkinetic seizures of frontal lobe origin preceded by left frontal spikes. We excluded linkage to chromosome 2q36 and found a suggestion of linkage to chromosome 22q12 with a lod score of 2.64 (θ = 0) for marker D22S689.
Black and White, or Shades of Gray? Racial Labeling of Barack Obama Predicts Implicit Race Perception
Authors: Malahy Lori Wu , Sedlins Mara , Plaks Jason , Shoda Yuichi
Published: July 2010

The present research capitalized on the prominence and multiracial heritage of U.S. 2008 presidential election candidate Barack Obama to examine whether individual differences in classifying him as Black or as multiracial corresponded to differences in implicit perception of race. This research used a newly developed task (Sedlins, Malahy, & Shoda, 2010) with digitally morphed mixed‐race faces to assess implicit race perception. Participants completed this task four times before and one time after the election. We found that people who labeled Obama as Black implicitly perceived race as more categorical than those who labeled Obama as multiracial. This finding adds to the growing literature on multiracial perception by demonstrating a relationship between the explicit use of multiracial and monoracial race classification and implicit race perception. The results suggest potential implications for governmental, educational, and judiciary usage of racial categories.
Molecular monitoring and mutation analysis of patients with advanced phase CML and Ph+ ALL receiving dasatinib
Authors: Olsson‐Strömberg Ulla , Hermansson Monica , Lundán Tuija , Ohm Anne‐Charlotte , Engdahl Ida , Höglund Martin , Simonsson Bengt , Porkka Kimmo , Barbany Gisela
Published: July 2010

As a result of the excellent responses achieved in chronic phase chronic myeloid leukemia since the introduction of imatinib, sensitive techniques such as reverse transcriptase real‐time PCR are warranted to monitor patients receiving tyrosine kinase inhibitors (TKI). Our objective was to determine the value of molecular monitoring Ph‐positive leukemias under dasatinib treatment. We used real‐time PCR and ABL1 kinase domain sequencing on sequential samples from 11 patients with Philadelphia‐positive leukemias who received dasatinib. We were able to detect pre‐existing mutations in the kinase domain of BCR‐ABL1 in four patients, particularly in patients with high BCR‐ABL1 transcript levels. Most mutations disappeared with dasatinib, however, in five patients a clone with T315I appeared during dasatinib treatment. We conclude that sensitive molecular monitoring with real‐time PCR for BCR‐ABL1 transcripts and mutation screening of the ABL1 kinase domain of patients with Philadelphia‐positive leukemias are valuable for patient management, however, mutation findings should be interpreted with caution, as mutant clones not always behave in vivo as predicted by in vitro assays.
Dental agenesis: genetic and clinical perspectives
Authors: De Coster P. J. , Marks L. A. , Martens L. C. , Huysseune A.
Published: July 2010

Dental agenesis is the most common developmental anomaly in humans and is frequently associated with several other oral abnormalities. Whereas the incidence of missing teeth may vary considerably depending on dentition, gender, and demographic or geographic profiles, distinct patterns of agenesis have been detected in the permanent dentition. These frequently involve the last teeth of a class to develop (I2, P2, M3) suggesting a possible link with evolutionary trends. Hypodontia can either occur as an isolated condition (non‐syndromic hypodontia) involving one (80% of cases), a few (less than 10%) or many teeth (less than 1%), or can be associated with a systemic condition or syndrome (syndromic hypodontia), essentially reflecting the genetically and phenotypically heterogeneity of the condition. Based on our present knowledge of genes and transcription factors that are involved in tooth development, it is assumed that different phenotypic forms are caused by different genes involving different interacting molecular pathways, providing an explanation not only for the wide variety in agenesis patterns but also for associations of dental agenesis with other oral anomalies. At present, the list of genes involved in human non‐syndromic hypodontia includes not only those encoding a signaling molecule (TGFA) and transcription factors (MSX1andPAX9) that play critical roles during early craniofacial development, but also genes coding for a protein involved in canonical Wnt signaling (AXIN2), and a transmembrane receptor of fibroblast growth factors (FGFR1). Our objective was to review the current literature on the molecular mechanisms that are responsible for selective dental agenesis in humans and to present a detailed overview of syndromes with hypodontia and their causative genes. These new perspectives and future challenges in the field of identification of possible candidate genes involved in dental agenesis are discussed.
Power and metabolic responses during supramaximal exercise in 100‐m and 800‐m runners
Authors: Denis C. , Linossler M. T. , Dormols D. , Padilla S. , Geyssant A. , Lacour J. R. , Inbar O.
Published: July 2010

The differences in ergometric power and in biochemical characteristics of the vastus lateralis muscle (VL) between 100‐m and 800‐m runners (R) were studied in 2 groups of 8 male athletes (100m‐R and 800m‐R) during a 45‐s all‐out cycle ergometer exercise. Peak power (PP), mean power (MP) and percentage of fatigue were respectively 24%, 13% and 24% higher in the 100m‐R than in 800m‐R, whereas total work output was similar in both groups. In 100m‐R, there was a higher percentage of fast twitch (FT) fibres, a higher buffer (mß) titration capacity and a lower oxidative potential expressed by citrate synthase, 3‐hydroxyacyi‐CoA dehydrogenase and cytochrome oxidase than in 800m‐R. During all‐out exercise, muscle lactate [lact] and protons [H+] accumulated significantly more in 100m‐R than in 800m‐R with a corresponding muscle pH of 6.49 ± 0.07 and 6.63 ± 0.12. However, the decreases in adenosine triphosphate (ATP) and creatine phosphate were not different between the two groups. Significant correlations were found between PP (or % fatigue) and Δ[H+], Δ[lact], Δ[ATP], %FT or oxidative capacity when the two groups were pooled together. It was concluded mat the difference in %FT, in titration mß and in the contribution of the glycolytic and oxidative processes observed in VL between 100m‐R (pure anaerobic training) and 800m‐R (mixed aerobic‐anaerobic training) are determinant factors in the pattern of energy output during supramaximal exercise.
Cardiac rehabilitation today: programs, their effects and practical guidelines
Authors: Ekelund L. G. , Ekelund C. C.
Published: July 2010

Cardiac rehabilitation programs started to develop in the early 1970s. At that time the emphasis was on physical training. The goal was early return to work and lowering of mortality. Today, cardiac rehabilitation also includes risk factor modification and stress management. From 1972 to 1986, 22 randomized, controlled trials were performed to evaluate whether cardiac rehabilitation would be able to decrease mortality and improve people's ability to return to work. Although all of them reported an increase in physical working capacity, only one reported a decrease in mortality. However, a meta‐analysis of the 22 trials was reported in 1989. The study found a 20% decrease in total mortality and a 22% decrease in cardiovascular mortality, both significant. This article describes the principles of cardiac rehabilitation and different types of program models with a detailed description of 3 different programs. It also reviews the effect of cardiac rehabilitation on mortality and its use in primary prevention.
Preoccupation with weight and menstrual function in female elite athletes
Authors: Sundgot‐Borgen J. , Larsen S.
Published: July 2010

To determine the self‐reported prevalence of menstrual dysfunction in athletes and controls found to be at risk of developing eating disorders (ED) and the factors characterizing and classifying athletes suffering from menstrual dysfunction, the Eating Disorder Inventory (EDI) and a self‐developed questionnaire were administered to the total population of Norwegian female elite athletes (n=603) and age‐ and home community‐matched controls (n=522). The response rate in both athletes and controls was 86%. Subjects younger than 16 years who had not attained menarche (29 athletes and 14 controls) and subjects taking contraceptive medication (145 athletes and 131 controls) were excluded. Thus, a total of 348 athletes (19.4±4.3 years) and 303 controls (20.6±4.4 years) were analyzed. A high prevalence of athletes (42%) reported menstrual dysfunction; the prevalence of menstrual dysfunction was significantly different between subjects classified as at risk of developing ED (54% and 36%, for athletes and controls, respectively) and subjects found not to be at risk (41% and 23%, respectively). Furthermore, the prevalence of menstrual dysfunction was significantly higher among athletes competing in sports in which leanness and/or a specific weight are considered important (endurance: 62%, aesthetics: 60% and weight‐dependent: 50%) than among athletes competing in sports in which these factors are considered less important (technical: 37%, ballgames: 28% and power sports: 22%). Menarchal age, training volume, body mass index (BMI) and EDI score contributed significantly to explaining menstrual dysfunction in athletes (37%). The authors suggest that athletes reporting menstrual dysfunction could be characterized and classified into 2 main groups: first, the athletes who have a predisposed genetically lean body build (low BMI) and a delayed menarche and undertake hard physical training that does not allow them to achieve the “critical” weight for height found necessary for regular cycles. Secondly, the athletes who have normal BMI, experience menarche at the expected time and who become preoccupied with weight and dieting and/or use of pathogenic weight control methods which then, at least in part, may explain the menstrual dysfunction.
High‐altitude training does not increase maximal oxygen uptake or work capacity at sea level in rowers
Authors: Jensen K. , Nielsen T. S. , Fiskestrand A. , Lund J. O. , Christensen N. J. , Sechef N. H.
Published: July 2010

Maximal oxygen uptake (Vo2max was evaluated after high‐altitude training in rowers. Nine rowers trained in a camp at 1822 m for 3 weeks with no change in Vo2max or 6‐min work capacity on a rowing ergometer at sea level. In contrast, 9 control rowers training at sea level increased Vo2max by 4 (0‐8)% and work capacity by 3 (0‐11)% (median and range). In rowers emphasizing endurance training during a summer of competitive rowing (n=9), Vo2max and work capacity increased by 6 (0‐13)% and 3 (‐1‐6)%, respectively and no significant changes were noted in rowers performing interval training (n= 9). Exhaustive rowing on an ergometer was characterized by elevated plasma adrenaline, noradrenaline (n=13) and lactate (n=14) (to 19 (11‐31), 74 (50‐109) nmol l1 and 15 (11‐22) mmol‐I1, respectively). In heavyweight rowers (n=11), blood volume was 7.0 (5.9‐8.3) litres, left ventricular wall thickness 13 (11‐15) mm and end‐diastolic diameter 57 (54‐66) mm (n=11). This study demonstrated an elevated blood volume in rowers as well as myocardial hypertrophy and large internal heart diameters. In well‐trained rowers, endurance training is superior to interval training for elevating Vo2max and work capacity, but high‐altitude training does not contribute to increasing Vo2max or work capacity at sea level.
Effects of training, immobilization and remobilization on tendons
Authors: Kannus P. , Józsa L. , Natri A. , Järvinen M.
Published: July 2010

Since a tendon is a living tissue, it is not a surprise that tendon shows the capacity to adapt its structure and mechanical properties to the functional demands of the entire muscle‐tendon unit. However, compared with muscle, the experimental knowledge of the effects of strength or endurance‐type training on tendon tissue is scarce and clinical human experiments are completely lacking (1). Research should, however, be able to improve the true understanding of the biomechanical, functional, morphological and biochemical changes that occur in tendons due to training and physical activity, since understanding of the basic physiology of a tissue is the key to understanding its pathological processes (1,2). Compared with muscle tissue, the metabolic turnover of tendon tissue is many times slower due to poorer vascularity and circulation (1, 3). The adaptive responses of tendons to training are therefore also slower than those in muscles, but they may finally be considerable if the time frame is long enough (3, 4).
Ultrasonography‐guided percutaneous core biopsy in Achilles tendon disorder
Authors: Movin T. , Guntner P. , Gad A. , Rolf C.
Published: July 2010

Ultrasound‐guided percutaneous core biopsy technique was studied in 15 consecutive patients with chronic Achilles tendon disorder defined as persisting local pain during daily activities, localized pain and swelling on palpation 2‐5 cm proximal to the calcaneal insertion. Ultrasound verified widening of the tendon and low echogenous areas at the site of pain. Percutaneous biopsies were taken from both the low echogenous areas and the normoechogenic tendon tissue. Of 104 core biopsies 99 were representative. Open biopsies were taken from the macroscopically injured and normal tendon for comparison. Core and open biopsies of the low echogenous and macroscopically injured tendon showed similar histopatology. In 10 patients the core biopsy was performed under local anesthesia with limited subjective symptoms. Five of these patients were operated 18–41 days later. No adverse effect was found referring to the biopsy taken a few weeks prior to surgery. No complications occurred. We conclude that the percutaneous core biopsy, guided by ultrasound and performed under local anesthesia, can be used under clinical and experimental in vivo studies for improving knowledge on pathoanatomy and healing processes of the Achilles tendon.
The physical activity level in children with asthma based on a survey among 7–16‐year‐old school children
Authors: Nystad W.
Published: July 2010

The objective was to compare the physical activity level of children with asthma with that of non‐asthmatic children. A standardized written questionnaire was administered in a survey of school children in three different areas of Norway: Oslo (n=2577), Hallingdal (n=831) and Odda (n= 1177). Response rates were >85% in all areas, and approximately 50% of the respondents were female. No significant differences were found between the distributions in exercise frequency either for children reported ever to have had asthma (P=0.8) or for those with current asthma (P=0.3) compared to non‐asthmatics. Similar results were found for exercise hours a week. More than 50% of all children took part in organized sport. The data suggest that asthmatic children are as physically active as their peers.
The association of physical activity level characteristics and other lifestyles with obesity in Nagoya University alumni, Japan
Authors: Fujii T. , Ohsawa I. , Nozawa A. , Mori K. , Kagaya M. , Kajioka T. , Oshida Y. , Sato Y.
Published: July 2010

Improving daily‐life habits is considered to be effective in treating obesity. We have examined obesity in regular physical examinations in university students since 1974. In this study, the subjects were 199 students regarded as obese (Broca's index: more than 120%) and 326 non‐obese students randomly selected (525 subjects in total) among students who underwent regular physical examinations at Nagoya University, Japan, between 1974 and 1978. Here we report our follow‐up survey of obese university students and non‐obese individuals who were students of the same university during the same period. This study was carried out for the purpose of clarifying the relationship between changes in lifestyle and body weight 20 years after graduation. Concerning eating behavior, a higher proportion of subjects cared about diet intake in the current non‐obese group than in the current obese group (P < 0.05). The meal‐time in the obese was shorter than that in the non‐obese group (P < 0.01). Ten percent of subjects in the obese group and 24.4% of subjects in the non‐obese group selected class II (moderate) or higher as indicative of the intensity of their daily physical activity. There was a significant difference in distribution between the groups (P < 0.05). In the group showing improvement in obesity over time, a higher proportion of subjects cared about diet intake than in the group with continued obesity (P < 0.05). Concerning intensity of physical activity, 11.8% of subjects in the group with continued obesity selected class II (moderate) or higher, while 45.5% of subjects in the group showing improvement in obesity chose class II (moderate) or higher. A significant difference in distribution existed between the groups (P < 0.01). These findings suggest that the eating behavior of ending meals before feeling satiety and a lifestyle change to enhance the intensity of daily physical activity including walking, even if not having any special sports habits, are effective in decreasing body weight.
Effect of motivational climate profiles on motivational indices in team sport
Authors: Ommundsen Y. , Roberts G. C.
Published: July 2010

Contemporary perspectives of achievement motivation have been based on social cognitive theories which give motivational climate a central place in the regulation of subsequent affective states, cognitions and behaviour in achievement contexts. This study examined the relationship between different profiles of the motivational climate in team sport and achievement, and socially related cognitions among Norwegian team sport athletes. Players (N= 148) assessed their perception of the motivational climate using the Norwegian version of the Motivational climate in sport questionnaire, sources of satisfaction in team sport, achievement strategies, perceived purposes of sport, and conceptions of ability. Multi‐variate analysis of variance (2×2) showed both main effects for profiles of the motivational climate and an interaction effect. Athletes perceiving the climate as high in mastery and high in performance oriented criteria reported psychological responses that were more adapative than those perceiving the climate as low in mastery and high in performance criteria. With one exception, the findings showed that those high in mastery and low in performance were more likely to emphasise self‐referenced criteria when judging perceived ability in team sport. For both social responsibility and lifetime skills as purposes in sport, it was the high performance and low mastery athletes who were least likely to endorse these purposes. And importantly, the high mastery climate seemed to moderate the impact of being in a high performance climate. The pattern of findings suggests that perceiving the motivational climate as performance oriented may not be motivationally maladaptive when accompanied by mastery oriented situational cues.
Myocardial response to a triathlon in male athletes evaluated by Doppler tissue imaging and biochemical parameters
Authors: Leetmaa T. H. , Dam A. , Glintborg D. , Markenvard J. D.
Published: July 2010

The aim of this study was to examine cardiac dysfunction following ultra‐endurance exercise in male athletes. Fourteen athletes (mean±SD, age 39±8 years) were evaluated before and after the European Championship in Triathlon 2003 using echocardiogram (ECG), cardiac markers [cardiac troponin T (cTnT) and pro‐brain natriuretic peptide (pro‐BNP)] and echocardiography. Conventional echocardiography techniques and new Doppler tissue imaging (DTI) modalities were applied before and immediately after the competition. Blood samples were drawn 1 week before, immediately after and 12–24 h post‐competition. CTnT significantly increased immediately, but decreased to within normal limits 12–24 h post‐competition. Pro‐BNP was significantly increased immediately post‐race (27±21 vs 7±2 pmol/L pre‐race, P≤0.007), which 12–24 h later, decreased to 19±14 pmol/L (P=0.07 vs pre‐race). During echocardiography, no significant differences were found in regional or global systolic parameters. Early diastolic peak flow velocity (9±2, P=0.04) and E/A ratio (2±1, P=0.004) were increased pre‐race and decreased significantly toward normal values. In one athlete, cTnT levels increased significantly and systolic velocities decreased, thus suggesting reversible cardiac fatigue. When using cardiac markers and echocardiographic findings, a triathlon was found to have no significant negative effects on left ventricular function or myocardial tissue in male athletes.
Reproducibility and changes in twitch properties associated with age and resistance training in young and elderly women
Authors: Cannon J. , Kay D. , Tarpenning K. M. , Marino F. E.
Published: July 2010

We compared knee extensor twitch contractile properties (TP) between nine young women (YW, 20–30 years) and 10 elderly women (63–78 years) and examined changes associated with resistance training in addition to measurement reproducibility. Data were obtained on two occasions 3 weeks apart after which subjects performed bilateral leg extension and bilateral leg curl exercises 3 days/week for 10 weeks. TP demonstrated moderate to good reproducibility in both age groups with Pearson's r and the intra‐class correlation coefficient ranging from 0.67 to 0.85 (P<0.05) and the technical error of the measurement ranging from 4.2% to 7.8%. Pre‐training, peak twitch torque, rate of torque development, and the rate of relaxation were 24–32% greater for the YW than EW (P<0.05). Time to peak torque, half‐relaxation time, and contraction duration were not significantly different between age groups. Post‐training, changes of 2.6–6.1% were observed in TP; however, these changes were not significant in either group. These data suggest the presence of an age‐associated slowing in the rate of muscle contraction. Furthermore, the lack of change in TP in both groups suggests resistance training failed to alter contractile function. However, these findings are discussed in relation to measurement reproducibility and the meaningfulness of the data obtained.
Physical activity in leisure‐time is not associated with 10‐year changes in waist circumference
Authors: Berentzen T. , Petersen L. , Schnohr P. , Sørensen T. I. A.
Published: July 2010

To examine whether physical activity (PA) is associated with changes in waist circumference (WC), and changes in WC given changes in body mass index (BMI). Longitudinal population‐based study including 2026 men and 2782 women aged 21–81 years. Subjects were examined in 1991–1993 (baseline) and 2001–2003 (follow up), where height, weight and WC were measured. Information about overall PA in leisure‐time (LTPA), walking, biking and sports activity was collected with self‐administrated questionnaires at baseline. Outcomes were changes in WC and changes in WC given changes in BMI between baseline and follow up. The median increase in WC was 3.0 cm in men and 3.5 cm in women during follow‐up, and with a considerable inter‐individual variation. LTPA, walking and biking were not significantly associated with the outcomes. Inverse associations between sports activity and the outcomes were observed in both sexes, and these were significant in some analyses. Associations were not altered by adjustment for confounders or by exclusions of subjects with diseases and/or treatment by obesity‐inducing medication. This study suggests that LTPA, walking and biking have no appreciable effects on changes in WC or changes in WC given changes in BMI, whereas sports activity may have small preventive effects.
Can we predict top‐level sports performance in power vs endurance events? A genetic approach
Authors: Buxens A. , Ruiz J. R. , Arteta D. , Artieda M. , Santiago C. , González‐Freire M. , Martínez A. , Tejedor D. , Lao J. I. , Gómez‐Gallego F. , Lucia A.
Published: July 2010

The goal of our study was to discriminate potential genetic differences between humans who are in both endpoints of the sports performance continuum (i.e. world‐class endurance vs power athletes). We used DNA‐microarray technology that included 36 genetic variants (within 20 different genes) to compare the genetic profile obtained in two cohorts of world‐class endurance (N=100) and power male athletes (N=53) of the same ethnic origin. Stepwise multivariate logistic regression showed that the rs1800795 (IL6−174 G/C), rs1208 (NAT2 K268R) and rs2070744 (NOS3−786 T/C) polymorphisms significantly predicted sport performance (model χ2=25.3, df=3, P‐value <0.001). Receiver–operating characteristic (ROC) curve analysis showed a significant discriminating accuracy of the model, with an area under the ROC curve of 0.72 (95% confidence interval: 0.66–0.81). The contribution of the studied genetic factors to sports performance was 21.4%. In summary, although an individual's potential for excelling in endurance or power sports can be partly predicted based on specific genetic variants (many of which remain to be identified), the contribution of complex gene–gene interactions, environmental factors and epigenetic mechanisms are also important contributors to the “complex trait” of being an athletic champion. Such trait is likely not reducible to defined genetic polymorphisms.
Low flow oxygenation of full‐excisional skin wounds on diabetic mice improves wound healing by accelerating wound closure and reepithelialization
Authors: Asmis Reto , Qiao Mu , Zhao Qingwei
Published: July 2010

Oxygen‐based therapies have proven effective in treating chronic and difficult‐to‐heal skin wounds, but the current therapeutic approaches suffer from major limitations and they do not allow for continuous wound treatment. Here we examined whether the continuous treatment of wounds with pure oxygen at low flow rates accelerates wound closure and improves wound healing in a murine model of diabetic skin wounds. Two full‐excisional dorsal skin wounds were generated on 15‐week‐old diabetic db/db mice and treated for 10 weeks continuously with pure oxygen (>99·9%) at low flow rates (3 ml/h). After 6 days, oxygen treatment resulted in a mean reduction of the original wound size by 60·2% as compared with only 45·2% in wounds on control mice that did not receive pure oxygen.(P = 0·022). After 10 days, oxygen‐treated wounds were 83·1% closed compared with 71·2% in wounds on control mice. While reepithelialisation was complete after 10 days in over 57% of wounds receiving low flow oxygen treatment, significant epithelial gaps remained in 75% wounds from mice that did not receive oxygen. Continuous low flow oxygenation significantly improves healing of diabetic skin wounds in mice and may therefore be an effective treatment for chronic cutaneous and possibly other slow‐healing wounds in diabetic patients.
Coalition: A new era in British politics
Authors: Muir Rick
Published: July 2010

Rick Muir assesses what the first peace‐time coalition government since the 1930s could mean for Britain.
The centre of central government
Authors: Blick Andrew , Jones George
Published: July 2010

Andrew Blick and George Jones examine the recent surge of interest in the structure and functioning of the‘centre of central government’ in the United Kingdom — Number 10, the Cabinet Office and the Treasury. They ask if it is fit for purpose and make recommendations for its future.
Why do childcare markets fail?: Comparing England and the Netherlands
Authors: Lloyd Eva , Penn Helen
Published: July 2010

In the last 10 years governments in England and the Netherlands have vigorously encouraged the growth of childcare markets but the very concept of a childcare market is problematic, contend Eva Lloyd and Helen Penn
The new Penguin enclosure at Edinburgh Zoo: the Palace for the 1990s
Authors: STEVENSON MIRANDA F. , DRYDEN HOWARD , ALABASTER AMANDA , WREN COLIN
Published: July 2010

Penguins have been exhibited at Edinburgh Zoo since 1914 and the Zoo is well‐known for its expertise in keeping and breeding these birds, in particular the King penguin Aptenodvtes patagonica and Gentoo penguin Pygoscelis papua. Remodelling and extension of the existing penguin enclosure was completed in 1992 and a young group of Macaroni penguins Eudyptes chrysolophus has been added to the exhibit. The new enclosure is believed to be the largest penguin enclosure in existence and the larger and deeper pool has allowed the birds greater opportunity for swimming. The condition of King and Gentoo penguins has visibly improved and both species have produced young in the two breeding seasons since the reopening. In this paper the planning and design of the enclosure and water filtration is described, together with brief notes on the management of the birds.
MEDIEVAL ENGLISH PARLIAMENTS
Authors: MILLER EDWARD
Published: July 2010

The English Parliament in the Middle Ages. By H. G. Richardson and G. O. Sayles. London: Hambledon Press

The English Parliament in the Middle Ages. Edited by R. G. Davies and J. H. Denton. Manchester: Manchester University Press
The Lost Leader: Sir Stafford Northcote and the Leadership of the Conservative Party, 1876–85*
Authors: KEOHANE NIGEL THOMAS
Published: July 2010

Sir Stafford Northcote has gone down in history as a man who fell short of the ultimate achievement of being prime minister largely because of personal weakness, and lack of political virility and drive. The picture painted by Northcote's political enemies – most notably the Fourth Party – has been accepted uncritically. Yet, political motives lay behind the actions of these supporters, and their harsh black and white portrait is not illustrative of the complexity of the situation in which Northcote found himself. Although individual characteristics undoubtedly played a part in his final political failure, underlying dynamics and structural transformations in politics and political life were more significant. It was more than simply the misfortune in succeeding the exceptionally charismatic Disraeli as leader. Northcote was faced with unparalleled disruption in parliament from Irish Nationalist MPs; the starkly polarised debate on the eastern question left him detached as a moderate. His temperament was better suited to constructive government rather than to opposition. However, following general election defeat in 1880, Northcote was denied this opportunity. Equally, his position in the lower House denied him the capacity to define a clear political critique of the Liberal government. Northcote's leadership of the party reflected the changing nature of British politics as radicals, tories, Irish Nationalists and Unionists increasingly contested the consensual style more appropriate to the political world of Palmerston and the 14th earl of Derby.
In Memory of Patrick Sourander (1917–1993)
Authors: Olsson Yngve
Published: July 2010

Patrick Sourander was the Professor of Neuropathology at the University of Göteborg, Sweden, who died on September 28,1993. His scientific interests focused on metabolic disturbances, in particular leucodystrophies, lipidosis and the consequences of malnutrition. He was the co‐discoverer of an inherited cerebrovascular disease now termed CADASIL (cerebral autosomal dominant arterio‐pathy with subcortical infarcts and leuokoencephalopathy). Earlier than many contemporary neuropathologists, Patrick Sourander realized the potential of a close cooperation between basic neurobiology and clinical investigations. As a founding member of the International Society of Neuropathology, Patrick held the office of Vice‐President during 1974–1978 and was the President of the Xth International Congress of Neuropathology held in Stockholm, in 1986.
Astrocytic Factors Deactivate Antigen Presenting Cells that Invade the Central Nervous System
Authors: Hailer Nils P. , Heppner Frank L. , Haas Dorit , Nitsch Robert
Published: July 2010

We hypothesized that CNS tissue has the potential to deactivate invading monocytes/macrophages in order to maintain the immune privilege of the brain, and furthermore, that astrocytes are the cells that initiate monocyte/macrophage deactivation. To test this hypothesis, fluorescent prelabeled rat spleen macrophages with typical amoeboid morphology were transferred into organotypic hip‐pocampal slice cultures (OHSCs), where they gradually developed a ramified morphology similar to the appearance of resting microglial cells. This morphological transformation also occurred if macrophages or monocytes were co‐cultured with mixed glial cultures or with astrocytoma cells, and ramification was accompanied by reduced expression of adhesion molecules leukocyte function antigen (LFA)‐1, intercellular adhesion molecule (ICAM)‐1, and major histocompatibility complex (MHC)‐class‐II molecules. Moreover, treatment of macrophages with astrocyte culture supernatant effectively down‐regulated the LPS‐induced expression of adhesion‐ and MHC‐class‐II‐molecules. Astrocyte supernatant‐induced inhibition of adhesion and MHC‐class‐II‐molecule expression was mimicked by transforming growth factor (TGF)‐β1, furthermore, this inhibitory effect was diminished by simultaneous treatment with neutralizing anti‐TGF‐β‐antibodies. In conclusion, our results suggest that astrocyte‐derived, soluble factors that are present in the CNS microenvironment deactivate invading macrophages, thus contributing to the maintenance of CNS immune‐privilege following impairment of blood‐brain‐barrier (BBB) integrity.
Apolipoprotein E Isoforms Increase Intracellular Ca2+ Differentially Through a ω‐Agatoxin IVa‐Sensitive Ca2+‐Channel
Authors: Müller W. , Meske V. , Berlin K. , Scharnagl H. , März W. , Ohm T.G.
Published: July 2010

Apolipoprotein E (apoE) is the major apolipoprotein in the brain and is known for its important role in plasticity and neurodegeneration. We show that apoE dose‐dependently increases intracellular free Ca2+ in rat hippocampal astrocytes and neurons. This effect varies with isoforms in the order E4>E3>E2. It is insensitive to blockade of action potentials by tetrodotoxin or inhibition of binding of apoE by heparinase, by the LRP ligand lactoferrin and by low density lipoprotein. ApoE evoked Ca2+‐increases are blocked in zero [Ca]o and by the Ca‐channel antagonists nickel and ω‐Agatoxin‐IVa but not by nifedipine and ω‐Conotoxin‐GVIa, demonstrating an isoform‐specific activation of P/Q type Ca2+‐channels. This novel mechanism is discussed with respect to Alzheimer's disease, that is linked for most cases to the apoE ε‐allelic variation (ε4 > ε3 > ε2).
Nerve Injury, Axonal Degeneration and Neural Regeneration: Basic Insights
Authors: Stoll Guido , Müller Hans Werner
Published: July 2010

Axotomy or crush of a peripheral nerve leads to degeneration of the distal nerve stump referred to as Wallerian degeneration (WD). During WD a microen‐vironment is created that allows successful regrowth of nerve fibres from the proximal nerve segment. Schwann cells respond to loss of axons by extrusion of their myelin sheaths, downregulation of myelin genes, dedifferentiation and proliferation. They finally aline in tubes (Büngner bands) and express surface molecules that guide regenerating fibres. Hematogenous macrophages are rapidly recruited to the distal stump and remove the vast majority of myelin debris. Molecular changes in the distal stump include upregulation of neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors and their corresponding receptors. Axonal injury not only induces muscle weakness and loss of sensation but also leads to adaptive responses and neuropathic pain. Regrowth of nerve fibres occurs with high specificity with formerly motor fibres preferentially reinnervating muscle. This involves recognition molecules of the L2/HNK‐1 family. Nerve regeneration occurs at a rate of 3–4 mm/day after crush and 2–3 mm/day after sectioning a nerve. Nerve regeneration can be fostered pharmacologically. Upon reestablishment of axonal contact Schwann cells remyelinate nerve sprouts and downregulate surface molecules characteristic for precursor/premyelinating or nonmyelinating Schwann cells. At present it is unclear whether axonal regeneration after nerve injury is impeded in neuropathies.
MHC Gene Related Effects on Microglia and Macrophages in Experimental Autoimmune Encephalomyelitis Determine the Extent of Axonal Injury
Authors: Storch Maria K. , Weissert Robert , Stefferl Andreas , Birnbacher Robert , Wallström Erik , Dahlman Ingrid , Ostensson Claes Göran , Linington Christopher , Olsson Tomas , Lassmann Hans
Published: July 2010

Myelin‐oligodendrocyte‐glycoprotein (MOG)‐induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG‐EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra‐RT1 recombinant rat strains with recombinations between the RT1a and RT1u haplotypes on the disease permissive LEW non‐MHC genome. Activated microglia and macrophages were identified morphologically and by expression of ED1 and allograft inhibitory factor‐1 (AIF‐1), and differentiated by their morphological phenotype. White matter lesions contained more macrophages and less microglia compared to grey matter lesions. Similarly active lesions were mainly infiltrated by macrophages, while microglia were abundant in inactive demyelinated plaques. In addition, we found a highly significant genetic association between a macrophage or microglia dominated lesional phenotype, which was independent from location and activity of the lesions. This was not only the case in demyelinating plaques of chronic EAE, but also in purely inflammatory lesions of acute passive transfer EAE. Rat strains with an u‐haplotype in both the Class II and the telomeric non‐classical Class I region revealed inflammatory and demyelinating lesions, which were dominated by activated microglia. The a‐haplotype in any of these regions was associated with macrophage dominated lesions. A comparison of lesions, exactly matched for stages of demyelinating activity in these different rat strains, showed that in spite of a similar extent of demyelination, axonal injury was significantly less in microglia compared to macrophage dominated lesions. Thus, our studies document a genetic influence of the MHC‐region on the relative contribution of macrophages versus microglia in the pathogenesis of EAE.
CADASIL: a Common Form of Hereditary Arteriopathy Causing Brain Infarcts and Dementia
Authors: Kalimo Hannu , Ruchoux Marie‐Magdaleine , Viitanen Matti , Kalaria Raj N.
Published: July 2010

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to cognitive decline and dementia. CADASIL usually begins with migraine in about one third of the patients. More severe manifestations, transient ischemic attacks or recurrent strokes, appear between 30 and 50 years of age. CADASIL, however, may be diagnosed well before the first stroke on the basis of characteristic white matter hyperintensities upon magnetic resonance imaging and presence of pathognomonic granular osmiophilic material in arterial walls, including dermal arteries, since the arteriopathy is generalized. Gradual destruction of vascular smooth muscle cells (VSMC) leads to progressive wall thickening and fibrosis and luminal narrowing in small and medium‐sized penetrating arteries. The reduced cerebral blood flow finally causes lacunar infarcts, mainly in the basal ganglia and fronto‐temporal white matter, which lead to cognitive deficits and dementia of the subcortical vascular type. CADASIL is caused by single missense mutations or small deletions in Notch3 gene encoding a transmembrane receptor Notch3, of which upon ligand binding a nuclear signaling protein is generated by regulated intramembrane proteolysis. Notch signaling is essential during development, regulating cellular differentiation. In adults Notch3 is expressed only in VSMCs and it may promote cell survival by inhibiting apoptosis, but its exact function is unknown. Mutations result in either a gain or loss of one (or rarely, 3) cysteine residue(s) in one of the 34 epidermal growth factor‐like repeats in the extracellular amino‐terminal region of Notch3. It is as yet unclear which disturbance in the Notch signaling pathway leads to the characteristic vascular pathology of CADASIL.
Collagen XVIII: a Novel Heparan Sulfate Proteoglycan Associated with Vascular Amyloid Depositions and Senile Plaques in Alzheimer's Disease Brains
Authors: van Horssen Jack , Wilhelmus Micha M. M. , Heljasvaara Ritva , Pihlajaniemi Taina , Wesseling Pieter , de Waal Robert M. W. , Verbeek Marcel M.
Published: July 2010

Heparan sulfate proteoglycans (HSPGs) may play a role in the formation and persistence of senile plaques and neurofibrillary tangles in Alzheimer's disease brains. Recently, it has been demonstrated that the human extracellular matrix‐associated molecule collagen XVIII is the first collagen carrying heparan sulfate side‐chains. Two variants of collagen XVIII with both different signal peptides and N‐terminal domains have been described and are referred to as the short and long form. To investigate the distribution of these variants we performed an immunohistochemical analysis by using specific well‐characterized polyclonal antibodies. Anti‐long huXVIII, a polyclonal antibody directed against the long variant of collagen XVIII, weakly stained large cortical and leptomeningeal vessels, whereas small cortical vessels remained unstained. Interestingly, all amyloid‐laden vessels and classic senile plaques were strongly stained. Anti‐all huXVIII, a polyclonal antibody directed against an epitope common to both collagen XVIII variants, intensely stained all types of cerebral blood vessels, cerebral amyloid angiopathy‐affected vessels and classic senile plaques. Collagen XVIII expression was absent in neurofibrillary tangles. We conclude that collagen XVIII is a novel heparan sulfate proteoglycan associated with vascular Aβ and classic senile plaques and that at least the long form of collagen XVIII accumulates in amyloid‐laden vessels and classic senile plaques.
Nitric Oxide in Traumatic Brain Injury
Authors: Cherian Leela , Hlatky Roman , Robertson Claudia S.
Published: July 2010

Nitric oxide (NO) is a gaseous chemical messenger which has functions in the brain in a variety of broad physiological processes, including control of cerebral blood flow, interneuronal communications, synaptic plasticity, memory formation, receptor functions, intracellular signal transmission, and release of neurotransmitters. As might be expected from the numerous and complex roles that NO normally has, it can have both beneficial and detrimental effects in disease states, including traumatic brain injury. There are two periods of time after injury when NO accumulates in the brain, immediately after injury and then again several hours‐days later. The initial immediate peak in NO after injury is probably due to the activity of endothelial NOS and neuronal NOS. Pre‐injury treatment with 7‐nitroindazole, which probably inhibits this immediate increase in NO by neuronal NOS, is effective in improving neurological outcome in some models of traumatic brain injury (TBI). After the initial peak in NO, there can be a period of relative deficiency in NO. This period of low NO levels is associated with a low cerebral blood flow (CBF). Administration of L‐arginine at this early time improves CBF, and outcome in many models. The late peak in NO after traumatic injury is probably due primarily to the activity of inducible NOS. Inhibition of inducible NOS has neuroprotective effects in most models.
Subclassification of Nerve Sheath Tumors by Gene Expression Profiling
Authors: Holtkamp Nikola , Reuß David E. , Atallah Isis , Kuban Ralf‐Jürgen , Hartmann Christian , Mautner Victor‐F. , Frahm Silke , Friedrich Reinhard E. , Algermissen Bernd , Pham Van‐Anh , Prietz Sandra , Rosenbaum Thorsten , Estevez‐Schwarz Lope , von Deimling Andreas
Published: July 2010

Nerve sheath tumors are the most common tumors of Neurofibromatosis type 1 (NF1) patients. Dermal neurofibromas develop in nearly all NF1‐patients, whereas plexiform neurofibromas are only observed in one‐third of the patients. NF1‐patients have about a 10% lifetime risk for developing malignant pheripheral nerve sheath tumors (MPNST). The origin of these tumors is thought to be the Schwann cell lacking functional neurofibromin. However, additional genetic alterations are likely to modulate tumor biology and to contribute to individual nerve sheath tumor entities. To gain insight into the molecular events and to determine whether these tumors can be classified according to gene expression profiles, we performed expression analysis applying cDNA array technology. Nine dermal neurofibromas, 7 plexiform neurofibromas, ten MPNST and two MPNST cell cultures were examined. All tumors but 6 sporadic MPNST were obtained from NF1‐patients. We detected significant differences in gene expression patterns between neurofibromas and MPNST and between dermal neurofibromas and plexiform neurofibromas. Tumor class prediction agreed in all but one case with histological and clinical classification. NF1‐associated and sporadic MPNST could not be distinguished by their gene expression patterns. We present a panel of discriminating genes that may assist subclassification of nerve sheath tumors.