bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of the polar {111} NaCl crystal face
Authors: Radenović Neda , Kaminski Daniel , van Enckevort Willem , Graswinckel Sander , Shah Ismail , in ’t Veld Mendel , Algra Rienk , Vlieg Elias
Published: April 2006

We present a surface x-ray diffraction determination of the {111} NaCl-liquid interface structure. Using ultrathin water or formamide liquid layers we ascertained that the crystal surface is smooth at an atomic level and is not reconstructed. Our results reveal surprisingly small differences in surface structure between the two cases, which nevertheless lead to dramatic differences in crystal morphology. We determined that the rocksalt {111} surface is Na+ terminated for both environmental conditions. A quarter to half a monolayer of laterally disordered Cl− ions is located on top of a fully ordered Na+ crystal surface with occupancy 0.75–1.0. This means that the polar surface is stabilized through the formation of an electrochemical double layer.
BRST quantization of quasisymplectic manifolds and beyond
Authors: Lyakhovich S. L. , Sharapov A. A.
Published: April 2006

We consider a class of factorizable Poisson brackets which includes almost all reasonable Poisson structures. A particular case of the factorizable brackets are those associated with symplectic Lie algebroids. The BRST theory is applied to describe the geometry underlying these brackets as well as to develop a deformation quantization procedure in this particular case. This can be viewed as an extension of the Fedosov deformation quantization to a wide class of irregular Poisson structures. In a more general case, the factorizable Poisson brackets are shown to be closely connected with the notion of n-algebroid. A simple description is suggested for the geometry underlying the factorizable Poisson brackets based on construction of an odd Poisson algebra bundle equipped with an Abelian connection. It is shown that the zero-curvature condition for this connection generates all the structure relations for the n-algebroid as well as a generalization of the Yang-Baxter equation for the symplectic structure.
Who Will See Me? The Impact of Type of Audience on Willingness to Display Group‐Mediated Attitude–Intention Consistency
Authors: Smith Joanne R. , Terry Deborah J. , Hogg Michael A.
Published: April 2006

The present study examined the role that group norms, group identification, and imagined audience (in‐group vs. out‐group) play in attitude–behavior processes. University students (N=187) participated in a study concerned with the prediction of consumer behavior. Attitudes toward drinking their preferred beer, subjective norm, perceived behavioral control, group norm, and group identification were assessed. Intentions and perceived audience reactions to consumption were assessed. As expected, group norms, identification, and imagined audience interacted to influence likelihood of drinking one's preferred beer and perceived audience reactions. High identifiers were more responsive to group norms in the presence of an in‐group audience than an out‐group audience. The present results indicate that audience concerns impact upon the relationship between attitudes and behavior.
Palatable Punishment in Real‐World Social Dilemmas? Punishing Others to Increase Cooperation Among the Unpunished1
Authors: Loukopoulos Peter , Eek Daniel , Gärling Tommy , Fujii Satoshi
Published: April 2006

Social‐dilemma research has shown that imposing sanctions on defection may increase cooperation, a principle behind attempts to solve real‐world social dilemmas. Yet sanctioning systems are often difficult to implement: They are unpopular and often have large surveillance and enforcement costs. A new sanctioning system, intentionally punishing defection intermittently for some but not all group members, is shown to increase cooperation among those not punished, a finding labeled thespillover effect. This study suggests that the effect cannot be attributed simply to cooperative tendencies, as factors affecting cooperation do not affect the effect's size. The benefits of such a sanctioning system, which preserves the characteristics of social dilemmas, could include minimization of surveillance and enforcement costs, and greater public acceptability.
Determination of the biliary excretion of piperacillin in humans using a novel method
Authors: Ghibellini Giulia , Vasist Lakshmi S. , Hill Terence E. , Heizer William D. , Kowalsky Richard J. , Brouwer Kim L. R.
Published: April 2006

Aim

To evaluate the applicability of a novel method to determine the biliary excretion of piperacillin.

Methods

Healthy volunteers were administered piperacillin i.v. Duodenal aspirates were collected via a custom‐made oroenteric catheter; blood and urine also were collected. Gallbladder ejection fraction (EF) was determined by gamma scintigraphy and pharmacokinetic parameters were calculated using noncompartmental analysis.

Results

The fraction of the piperacillin dose excreted unchanged into bile was 1.1 ± 0.3% (biliary clearance corrected for EF was 0.032 ± 0.008 ml min−1 kg−1).

Conclusions

This methodology can be used to determine reliably the biliary clearance of drugs that are excreted only marginally into bile. Normalization of biliary clearance for EF significantly reduces intersubject variability of this parameter.
Legislation restricting paracetamol sales and patterns of self‐harm and death from paracetamol‐containing preparations in Scotland
Authors: Bateman D. N. , Gorman D. R. , Bain M. , Inglis J. H. C. , House F. R. , Murphy D.
Published: April 2006

Aims

To describe how changes in legislation to restrict paracetamol sales have affected overdose discharges and death associated with the drug in Scotland.

Methods

A descriptive analysis of routine death and hospital discharge data for the entire Scottish population between 1995 and 2004. Patients in Scotland participated who were discharged from hospital with a diagnosis of poisoning; deaths in Scotland from diagnosis of poisoning 1995–2003 were also analysed. Outcome measures were changes in mortality and overdose due to poisoning involving paracetamol. A comparison was made of in‐hospital and out‐of‐hospital mortality in fatalities involving paracetamol.

Results

The majority of paracetamol‐associated deaths were due to co‐proxamol. Deaths associated with paracetamol alone or with ethanol occurred principally in hospital and were a minority of deaths overall. The proportion of in‐hospital deaths attributed to paracetamol increased (post/pre ratio 1.347; 95% confidence interval 1.076, 1.639;P = 0.013). Overall numbers of cases discharged with poisoning fell. The proportion of these involving paracetamol in any form increased significantly in all groups except young men aged 10 to <20 years.

Conclusions

Legislation has not reduced mortality or proportional use of paracetamol in overdose, both of which appear to have increased in Scotland since pack‐size limitations. Other approaches are necessary to reduce the death rate from overdoses involving paracetamol.
Novel mutations in the calcium‐sensing receptor gene associated with biochemical and functional differences in familial hypocalciuric hypercalcaemia
Authors: Ward Bryan K. , Magno Aaron L. , Blitvich Bradley J. , Rea Alexander J. , Stuckey Bronwyn G. A. , Walsh John P. , Ratajczak Thomas
Published: April 2006

Objective  Heterozygous inactivating mutations of the calcium‐sensing receptor (CaR) gene cause familial hypocalciuric hypercalcaemia (FHH), a generally benign disorder characterized by mild to moderate PTH‐dependent hypercalcaemia. We aimed to identify the causative CaR mutations in three families with FHH and examine the correlation between type of mutation and biochemical and/or functional phenotypes.

Patients, design and measurements  The CaR gene from FHH family members was assessed for mutations by direct DNA sequencing and mutations were confirmed by restriction enzyme analysis. Functional studies on two missense mutations were conducted by introducing them by site‐directed mutagenesis into the CaR cloned into a mammalian expression vector, and assessing calcium responsiveness using an inositol phosphate (IP) assay in HEK293 cells. Biochemical data from patients heterozygous for each type of mutant were correlated with functionality.

Results  Two novel nonsense mutations (R25stop and K323stop) and one novel missense mutation (G778D) were identified. The G778D mutant receptor and another mutation identified in an earlier study (L174R) demonstrated a complete lack of Ca2+ responsiveness using the IP assay. When cotransfected with wild‐type receptor, the mutant receptors demonstrated a dominant‐negative effect on wild‐type receptor response, with L174R having a more pronounced effect than G778D. Significantly more severe hypercalcaemia and a trend towards higher PTH levels were observed in patients heterozygous for CaR mutants with a stronger dominant‐negative effect.

Conclusions  Naturally occurring CaR mutations with differences in dominant‐negative effect on wild‐type receptor demonstrate differences in biochemical severity in FHH.
Risk factors associated with ixodid tick species distributions in the Basque region in Spain
Authors: Barandika J. F. , Berriatua E. , Barral M. , Juste R. A. , Anda P. , García‐Pérez A. L.
Published: April 2006

Abstract.  Ixodid tick abundance was investigated in the Basque region in Spain in two 1‐year longitudinal studies, in 1992–1993 and 2003–2004. Forty zones were visited monthly and 162 672 ticks (87% larvae, 12% nymphs and 1% adults) were collected by blanket dragging. Eleven tick species belonging to the genera Ixodes, Haemaphysalis, Rhipicephalus and Dermacentor were identified including Haemaphysalis concinna Koch, which had not previously been reported in Spain. Tick species abundance differed between zones, studies and seasons. In 1992–1993, Haemaphysalis punctata Canestrini & Fanzago was the predominant species and distinct spring–summer and autumn–early winter peaks of activity were observed. In 2003–2004, Ixodes ricinus (Linneaus) was the most common species and was active throughout the winter. Larval and nymph seasonal activity patterns coincided in both 1993 and 2003 and this could facilitate co‐feeding transmission of pathogens. Higher tick abundance was associated with increased livestock abundance in 1992–1993 and milder winter temperatures in 2003–2004. Tick collection rates in areas with moderate and high tick density were positively associated with the interaction between ambient temperature at sampling and rainfall 7 days prior to sampling. Collection rates were also significantly higher at medium rather than higher altitude, in forested areas than in open grasslands and lower in recreational areas frequented by people and with wet vegetation at sampling.
Evidence for a role of inducible nitric oxide synthase in gastric relaxation ofmdxmice
Authors: Mulè F. , Zizzo M. G. , Amato A. , Feo S. , Serio Rosa
Published: April 2006

Abstract Alterations of gastric mechanical activity have been reported inmdxmouse, animal model for Duchenne muscular dystrophy. This study examined if alterations in the vasoactive intestinal polypeptide (VIP) system are present inmdxstomach. Gastric mechanical activity was recordedin vitroas changes of endoluminal pressure and neurally or pharmacologically evoked relaxations were analysed inmdxvsnormal stomach. Reverse‐transcription polymerase chain reaction was used to detect inducible nitric oxide synthase (iNOS) expression. Relaxations to sodium nitroprusside inmdxstomach showed no difference in comparison with normal preparations. In normal stomach, VIP produced relaxation, which was reduced by VIP6‐28, antagonist of VIP receptors, but was not modified byN‐nitro‐l‐arginine methyl ester (l‐NAME), 1‐H‐oxodiazol‐[1,2,4]‐[4,3‐a]quinoxaline‐1‐one (ODQ) or byN‐(3‐(aminomethyl)‐benzyl)acetamidine (1400W) and aminoguanidine, inhibitors of iNOS. In contrast, inmdxstomach VIP responses were antagonized not only by VIP6‐28, but also byl‐NAME, ODQ, 1400W or aminoguanidine. In normal stomach, the slow relaxation evoked by stimulation at high frequency was reduced by VIP6‐28, but it was unaffected by 1400W or aminoguanidine. Inmdxstomach, it was reduced by VIP6‐28 or 1400W, which did not show additive effects. iNOS mRNA was expressed only inmdxstomach. The results suggest that inmdxgastric preparations, iNOS is functionally expressed, being involved in the slow relaxation induced by VIP.
Higher daytime leaf temperatures contribute to lower freeze tolerance under elevated CO2
Authors: LOVEYS BETH R. , EGERTON JOHN J. G. , BALL MARILYN C.
Published: April 2006

Elevated atmospheric CO2 adversely affects freezing tolerance in many evergreens, but the underlying mechanism(s) have been elusive. We compared effects of elevated CO2 with those of daytime warming on acclimation of snow gum (Eucalyptus pauciflora) to freezing temperatures under field conditions. Reduction in stomatal conductance gc under elevated CO2 was shown to cause leaf temperature to increase by up to 3 °C. In this study, this increase in leaf temperature was simulated under ambient CO2 conditions by using a free air temperature increase (FATI) system to warm snow gum leaves during daytime, thereby increasing the diurnal range in temperature without affecting temperature minima. Acclimation to freezing temperatures was assessed using measures of electrolyte leakage and photosynthetic efficiency of leaf discs exposed to different nadir temperatures. Here, we show that both elevated CO2 and daytime warming delayed acclimation to freezing temperatures for 2–3 weeks after which time freeze tolerance of the treated plants in both the FATI and open top chamber (OTC) experiments did not differ from control plants. Our results support the hypothesis that delayed development of freezing tolerance under elevated CO2 is because of higher daytime leaf temperatures under elevated CO2. Thus, potential gains in productivity in response to increasing atmospheric CO2 and prolonging the growing season may be reduced by an increase in freezing stress in frost‐prone areas.
Can fast‐growing plantation trees escape biochemical down‐regulation of photosynthesis when grown throughout their complete production cycle in the open air under elevated carbon dioxide?
Authors: DAVEY P. A. , OLCER H. , ZAKHLENIUK O. , BERNACCHI C. J. , CALFAPIETRA C. , LONG S. P. , RAINES C. A.
Published: April 2006

Poplar trees sustain close to the predicted increase in leaf photosynthesis when grown under long‐term elevated CO2 concentration ([CO2]). To investigate the mechanisms underlying this response, carbohydrate accumulation and protein expression were determined over four seasons of growth. No increase in the levels of soluble carbohydrates was observed in the young expanding or mature sun leaves of the three poplar genotypes during this period. However, substantial increases in starch levels were observed in the mature leaves of all three poplar genotypes grown in elevated [CO2]. Despite the very high starch levels, no changes in the expression of photosynthetic Calvin cycle proteins, or in the starch biosynthetic enzyme ADP‐glucose pyrophosphorylase (AGPase), were observed. This suggested that no long‐term photosynthetic acclimation to CO2 occurred in these plants. Our data indicate that poplar trees are able to ‘escape’ from long‐term, acclimatory down‐regulation of photosynthesis through a high capacity for starch synthesis and carbon export. These findings show that these poplar genotypes are well suited to the elevated [CO2] conditions forecast for the middle of this century and may be particularly suited for planting for the long‐term carbon sequestration into wood.
Prohibitin is involved in mitochondrial biogenesis in plants
Authors: Ahn Chang Sook , Lee Jeong Hee , Reum Hwang A , Kim Woo Taek , Pai Hyun‐Sook
Published: April 2006

Prohibitin, which consists of two subunits PHB1 and PHB2, plays a role in cell‐cycle progression, senescence, apoptosis, and maintenance of mitochondrial function in mammals and yeast. In this study, we examined the role of prohibitins in plants by using virus‐induced gene silencing (VIGS) of two prohibitin subunit genes of Nicotiana benthamiana, designated NbPHB1 and NbPHB2. NbPHB1 and NbPHB2 were targeted to the mitochondria, and their gene expression was suppressed during senescence. VIGS of NbPHB2 caused severe growth inhibition, leaf yellowing and symptoms of cell death, whereas VIGS of NbPHB1 resulted in a milder phenotype. At the cellular level, depletion of these subunits affected mitochondria by severely reducing their number and/or mass, and by causing morphological and physiological abnormalities. Suppression of prohibitin function resulted in a 10‐ to 20‐fold higher production of reactive oxygen species and induced premature leaf senescence. Finally, disruption of prohibitin function rendered the plants more susceptible to various oxidative stress‐inducing reagents, including H2O2, paraquat, antimycin A and salicylic acid. These results suggest that prohibitins play a crucial role in mitochondrial biogenesis and protection against stress and senescence in plant cells.
Comparison of the efficacy of rabeprazole 10 mg and omeprazole 20 mg for the healing rapidity of peptic ulcer diseases
Authors: Ji Sangwon , Kim Hyun Soo , Kim Jae Woo , Jee Myeong Kwan , Park Kwang Wha , Uh Young , Lee Dong Ki , Song Jae Suk , Baik Soon Koo , Kwon Sang Ok
Published: April 2006

Aim: Rabeprazole has been known to inhibit H+/K+‐ATPase more rapidly than omeprazole, the prototype proton pump inhibitor (PPI). The aim of this study was to demonstrate equivalence between low‐dose rabeprazole 10 mg and omeprazole 20 mg for the healing rapidity of active peptic ulcer and for improvement of symptoms. Also, the effect of CYP2C19 genotypes on ulcer healing rapidity was investigated.

Methods: A total of 112 patients with active peptic ulcer were randomized to receive either rabeprazole 10 mg q.d. or omeprazole 20 mg q.d. for 6 weeks. The remaining ratios (%) and complete healing of the ulcer were determined by endoscopy at 1 week and 6 weeks of treatment. The severity of ulcer pain was also investigated during treatment. CYP2C19 genotype was determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method.

Results: The remaining ratio of peptic ulcers after 1 week and the complete healing rate after 6 weeks in the rabeprazoleversusomeprazole group were 45.5%versus50.3% (P = 0.475) and 80.6%versus87.0% (P = 0.423), respectively. CYP2C19 genotypes had no effect on the remaining ratio of peptic ulcers after 1 week and the healing rate of peptic ulcers after 6 weeks in both groups. The proportions of patients with symptom improvement or resolution were comparable between the two groups.

Conclusion: Low‐dose rabeprazole 10 mg has a similar efficacy for the healing rapidity of active peptic ulcer disease and symptom improvement compared with standard‐dose omeprazole 20 mg.
Zinc L‐carnosine protects against mucosal injury in portal hypertensive gastropathy through induction of heat shock protein 72
Authors: Mikami Ken‐Ichiro , Otaka Michiro , Watanabe Daisuke , Goto Takashi , Endoh Ayako , Miura Kouichi , Ohshima Shigetoshi , Yoneyama Kazuo , Sato Michiko , Shibuya Tomomi , Segawa Daisuke , Kataoka Ei , Yoshino Ryutaro , Takeuchi Satoko , Sato Wataru , Odashima Masaru , Watanabe Sumio
Published: April 2006

Background and Aims:  Increased susceptibility to gastric mucosal injury is observed in portal hypertensive gastropathy (PHG). In this study, the effects of zinc L‐carnosine, an anti‐ulcer drug, were evaluated on expression of heat shock protein (hsp) 72 and cytoprotection in gastric mucosa in a rat model of PHG.

Methods:  Portal hypertensive gastropathy with liver cirrhosis was induced by bile duct ligation for 4 weeks in male Sprague–Dawley rats. Expression of gastric mucosal hsp72 was evaluated by Western blotting at 6 h after intragastric administration of L‐carnosine, zinc sulfate, or zinc L‐carnosine. Blood was also collected for determination of serum zinc level. Mucosal protective abilities against hydrochloric acid (HCl) (0.6N) followed by pretreatment with L‐carnosine, zinc sulfate or zinc L‐carnosine were also studied.

Results:  L‐carnosine, zinc sulfate, and zinc L‐carnosine induced hsp72 in gastric mucosa of rats with bile duct ligation. Zinc sulfate and zinc L‐carnosine suppressed HCl‐induced mucosal injury. However, L‐carnosine could not suppress HCl‐induced mucosal injury. Serum zinc levels were significantly elevated after zinc L‐carnosine administration. Furthermore, pretreatment with zinc L‐carnosine (30–300 mg/kg) increased the expression of hsp72 in gastric mucosa and prevented HCl‐induced mucosal injury in rats with bile duct ligation in a dose‐dependent manner.

Conclusions:  Zinc derivatives, especially zinc L‐carnosine, protected portal hypertensive gastric mucosa with increased hsp72 expression in cirrhotic rats. It is postulated that zinc L‐carnosine may be beneficial to the mucosal protection in PHG as a ‘chaperon inducer’.
Prevalence and risk factors of gallstone disease in an adult population of Taiwan: an epidemiological survey
Authors: Chen Chien‐Hua , Huang Min‐Ho , Yang Jee‐Chun , Nien Chiu‐Kue , Etheredge Gina Doskey , Yang Chi‐Chieh , Yeh Yung‐Hsiang , Wu Hurng‐Sheng ,   Der‐Aur Chou, Yueh Sen‐Kou
Published: April 2006

Background and Aims:  The aim of this study was to determine the prevalence and risk factors of gallstone disease (GSD) in an adult population of Taiwan through a population‐based screening study.

Methods:  A cross‐sectional community study in a rural village of Taiwan was conducted in 3333 Chinese adults (aged ≥18 years) undergoing ultrasonography. A questionnaire on personal history was completed to ascertain whether the removed gallbladder contained stones in all cholecystectomized subjects, the dietary habits (vegetarian/non‐vegetarian diet), the history of GSD in the participant’s first‐degree relatives, the history of gastrointestinal surgery (vagotomy, gastrectomy for peptic ulcer disease, or ileal resection), parity, and use of oral contraceptives. The demographic characteristics and biochemical parameters were recorded

Results:  The overall prevalence of GSD was 5.0% (4.6% in men, 5.4% in women) with no significant sex differences (men/women: odds ratio [OR] 0.71, 95% confidence interval [CI] 0.50–1.01, P = 0.058). Logistic regression analysis showed that increasing age (men: 40–64 years, OR 7.38, 95% CI 2.59–21.01, P < 0.001 and ≥65 years, OR 14.16, 95% CI 4.84–41.47, P < 0.001; women: 40–64 years, OR 4.08, 95% CI 1.90–8.75, P < 0.001 and ≥65 years, OR 6.78, 95% CI 2.97–15.46, P < 0.001) and the presence of fatty liver evidenced by ultrasonography (men: OR 2.24, 95% CI 1.32–3.80, P = 0.003; women: OR 2.13, 95% CI 1.33–3.42, P = 0.002) were risk factors for GSD. Additionally, fasting plasma glucose ≥126 mg/dL (OR 2.11, 95% CI 1.16–3.83, P = 0.014), history of GSD in the first‐degree relatives (OR 7.47, 95% CI 2.22–25.12, P = 0.001), and use of oral contraceptives (OR 10.71, 95% CI 3.06–37.49, P < 0.001) were risk factors for GSD in women, but fasting plasma glucose ≥126 mg/dL was only correlated to GSD without controlling for other confounding factors in men. Other demographic characteristics and biochemical parameters, such as high body mass index (≥25 kg/m2), increased parity, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, hepatitis C infection and cirrhosis, did not exhibit any correlation to GSD in logistic regression analysis, although they appeared to be related to GSD in women in univariate analysis.

Conclusions:  Age and fatty liver in both sexes were found to be risk factors for GSD in the study population. The finding of a correlation between fatty liver and GSD is an important addition to the literature concerning the risk factors of GSD. Diabetes mellitus, history of GSD in the first‐degree relatives, and use of oral contraceptives were also risk factors for GSD in women.
Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers
Authors: Ballermann Mark , Fouad Karim
Published: April 2006

Although injured axons in mammalian spinal cords do not regenerate, some recovery of locomotor function following incomplete injury can be observed in patients and animal models. Following a lateral hemisection injury of the thoracic spinal cord, rats spontaneously recover weight‐bearing stepping in the hind limb ipsilateral to the injury. The mechanisms behind this recovery are not completely understood. Plasticity in the reticulospinal tract (RtST), the tract responsible for the initiation of walking, has not been studied. In this study, rats received lateral thoracic hemisection of the spinal cord, and RtST projections were compared in two groups of rats, one early in recovery (7 days) and the other at a time point when weight‐bearing stepping was fully regained (42 days). We found that this recovery occurs in parallel with increased numbers of collaterals of spared RtST fibers entering the intermediate lamina below the injury at L2. Sprouting of injured RtST fibers above the lesion was not found. In conclusion, our study suggests that sprouting of spared RtST fibers might be involved in the recovery of locomotion following incomplete spinal cord injury.
Preservation of functional architecture in visual cortex of cats with experimentally induced hydrocephalus
Authors: Imamura Kazuyuki , Tanaka Shigeru , Ribot Jérôme , Kobayashi Masayuki , Yamamoto Masao , Nakadate Kazuhiko , Watanabe Yasuyoshi
Published: April 2006

We investigated how neural function is preserved or matured in the visual cortex of cats, following the induction of hydrocephalus by kaolin injection. In vivo optical imaging of intrinsic signals in 11–17‐week‐old hydrocephalic cats revealed orientation maps showing the orderly arrangement of preferred orientations when stimulated by grating stimuli at a low spatial frequency, whereas stimulus‐evoked intrinsic signals in response to gratings at a high spatial frequency were often too weak to construct orientation maps. Furthermore, in two of the three hydrocephalic cats, initially deteriorated orientation maps became almost regular maps in the second imaging experiments conducted 8 and 11 weeks, respectively, after the first imaging. This indicates that, despite large structural deformation of the hydrocephalic brain, orientation maps are elaborated sufficiently after the age of 5–6 months, by which time the orientation map formation is usually completed in normal cats. Single unit recording from the decompressed visual cortex revealed that many neurons showed normal orientation selectivity, whereas the binocularity of these neurons was found to be reduced. These results suggested that the deformed visual cortex of hydrocephalic cats exhibits a high plasticity, retaining its functional organization.
Epidemiology of headache in Europe
Authors: Stovner L. J. , Zwart J.‐A. , Hagen K. , Terwindt G. M. , Pascual J.
Published: April 2006

The present review of epidemiologic studies on migraine and headache in Europe is part of a larger initiative by the European Brain Council to estimate the costs incurred because of brain disorders. Summarizing the data on 1‐year prevalence, the proportion of adults in Europe reporting headache was 51%, migraine 14%, and ‘chronic headache’ (i.e. ≥15 days/month or ‘daily’) 4%. Generally, migraine, and to a lesser degree headache, are most prevalent during the most productive years of adulthood, from age 20 to 50 years. Several European studies document the negative influence of headache disorders on the quality of life, and health‐economic studies indicate that 15% of adults were absent from work during the last year because of headache. Very few studies have been performed in Eastern Europe, and there are also surprisingly little data on tension‐type headache from any country. Although the methodology and the quality of the published studies vary considerably, making direct comparisons between different countries difficult, the present review clearly demonstrates that headache disorders are extremely prevalent and have a vast impact on public health. The data collected should be used as arguments to increase resources to headache research and care for headache patients all over the continent.
Correlation of cognitive status, MRI‐ and SPECT‐imaging in CADASIL patients
Authors: Scheid R. , Preul C. , Lincke T. , Matthes G. , Schroeter M. L. , Guthke T. , Yves von Cramon D. , Sabri O.
Published: April 2006

Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc‐99m‐ethyl cysteinate‐dimer SPECT in three CADASIL patients. MR‐images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients’ history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural‐, or functional neuroimaging, nor by the patient‐specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials.
European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society
Authors: Hughes R. A. C. , Bouche P. , Cornblath D. R. , Evers E. , Hadden R. D. M. , Hahn A. , Illa I. , Koski C. L. , Léger J. M. , Nobile‐Orazio E. , Pollard J. , Sommer C. , Van den Bergh P. , Van Doorn P. A. , Van Schaik I. N.
Published: April 2006

Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment of CIDP. Disease experts and a patient representative considered references retrieved from MEDLINE and Cochrane Systematic Reviews in May 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (1) intravenous immunoglobulin (IVIg) or corticosteroids should be considered in sensory and motor CIDP (level B recommendation); (2) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (3) if IVIg and corticosteroids are ineffective plasma exchange (PE) should be considered (level A recommendation); (4) If the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (5) Symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).
The efficacy of excimer laser (308 nm) for vitiligo at different body sites
Authors: Hofer A , Hassan AS , Legat FJ , Kerl H , Wolf P
Published: April 2006

Background  The treatment with XeCl‐excimer laser generated 308‐nm UVB radiation has shown promising results in patients with vitiligo.

Objective  In this controlled, prospective trial we studied the primary efficacy (start and grade of repigmentation) and patient's satisfaction of XeCl‐excimer laser for treatment of vitiligo patches at different body sites and re‐evaluated the achieved repigmentation 12 months after the end of therapy.

Methods  Twenty‐five patients with generalized or localized vitiligo with a total of 85 lesions at different body sites were enrolled in this study. Vitiligo patches were treated with 308‐nm XeCl‐excimer laser 3 times a week for 6 to 10 weeks. The overall repigmentation grade of each treated lesion was evaluated once a week on a 5 point scale rating from 0 (no repigmentation), 1 (1–5%), 2 (6–25%), 3 (26–50%), 4 (51–75%), to 5 (76–100%).

Results  Twenty‐four patients completed the study. Within 6 to 10 weeks of treatment 67% of the patients (16/24) developed follicular repigmentation of at least one of their vitiligo lesions. Lesion repigmentation started after a mean of 13 treatments in lesions located on the face, trunk, arm, and/or leg (high‐responder location), and after a mean of 22 treatments in lesions located on the elbow, wrist, dorsum of the hand, knee, and/or dorsum of the foot (low‐responder location). Untreated control lesions and lesions located on the fingers did not achieve any repigmentation. After 10 weeks of treatment repigmentation of more than 75% was found in 25% (7/28) of lesions of the high‐responder location group versus 2% (1/43) of lesions of the low‐responder location group. In most cases, laser‐induced repigmentation was persistent, as determined 12 months after the end of treatment.

Conclusions  308‐nm excimer laser is an effective modality for the treatment of vitiligo. However, similar to other non‐surgical treatment modalities, the therapeutic effect is mainly dependent on the location of vitiligo lesions.
The usefulness of a diagnostic biopsy clinic in a genitourinary medicine setting: recent experience and a review of the literature
Authors: Palamaras I , Hamill M , Sethi G , Wilkinson D , Lamba H
Published: April 2006

Genital diseases include a wide range of lesions e.g. infectious and inflammatory. In most cases a clinical diagnosis is reached without the need for a biopsy. Nonetheless, a genital biopsy is safe and may help to confirm the diagnosis. We established a dedicated diagnostic biopsy clinic in 2003. Our objective was to evaluate the effectiveness of our diagnostic biopsy clinic and compare it with other Genitourinary medicine (GUM) clinics in the UK. A retrospective case‐note study was performed on 71 patients referred to the biopsy clinic with persistent genital lesions over a 12‐month period. Forty‐seven biopsies were performed (71% biopsy rate). 43 specimens (92%) were appropriate for histopathological diagnosis. Of these 15% were lichen planus, 15% lichen sclerosis, 10% psoriasis, 7.5% each: eczema, Zoon's and non‐specific balanitis. The remainder represented a variety of other conditions. In 27 cases (68%) the clinical diagnosis was consistent with the histological result.

The possibility of self‐referral and walk‐in nature of our GUM service substantially decrease the waiting times for assessment of anogenital disorders. We had a lower biopsy rate for the diagnosis of non‐specific balanitis (7.5%) compared with the average rate (21.5%) in 14 UK GUM clinics and good agreement between clinical and histological diagnosis. An empirical first treatment, with simple emollients before biopsy, appears to be a safe clinical approach for the treatment of non‐specific balanitis. A multidisciplinary approach (GUM physicians, dermatologists and urologists/gynaecologists) could help prevent unnecessary biopsies and improve correlation between clinical and histological diagnosis.
Genetically modified Lactococcus lactis: novel tools for drug delivery
Authors: STEIDLER LOTHAR , VANDENBROUCKE KLAAS
Published: April 2006

The dairy bacterium Lactococcus lactis can be genetically engineered to secrete bioactive cytokines. This enabled the development of an entirely novel drug delivery system: topical and active delivery of therapeutic proteins by genetically modified micro‐organisms. In mice, intestinal inflammation can be successfully treated with interleukin‐10‐ (IL‐10) or trefoil factor‐secreting L. lactis. In human application, biological containment is guaranteed by exchange of the gene encoding thymidylate synthase for IL‐10. The recombinant strain is now absolutely dependent on exogenous thymidine. Thymidine starvation will irreversibly lead to ‘thymidine‐less death’ induction. This accomplishment has opened applications in human medicine.
A neuroactive steroid 5α‐androstane‐3α,17β‐diol regulates androgen receptor level in astrocytes
Authors: Agapova Olga A. , Malone Paula E. , Hernandez M. Rosario
Published: April 2006

Optic nerve head (ONH) astrocytes from patients with glaucomatous optic neuropathy exhibit increased production of 5α‐androstane‐3α,17β‐diol (3α‐diol), a neuroactive metabolite of 5α‐dihydrotestosterone (5α‐DHT). To determine whether ONH astrocytes are androgen target cells, and whether 3α‐diol is capable of regulating astrocyte functions, we studied the response of human ONH astrocytes to 3α‐diol compared with 17β‐hydroxy‐17α‐methyl‐estra‐4,9,11‐trien‐3‐one (R1881), a synthetic 5α‐DHT agonist. In ONH astrocytes, both 3α‐diol and R1881 increased protein levels of androgen receptor (AR) and glial fibrillary acidic protein (GFAP), however, only R1881 also increased the AR mRNA level and astrocyte proliferation. Both R1881 and 3α‐diol rapidly activate the mitogen‐activated protein kinase (MAPK) signaling pathway in ONH astrocytes, as confirmed by phosphorylation of extracellular signal‐regulated kinase (ERK). 3α‐diol also activates the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) pathway. 3α‐diol regulates the increase of AR protein level and the phosphorylation through the PI3K/Akt pathway, whereas R1881 regulates them through the MAPK/ERK pathway. Our findings demonstrate that human ONH astrocytes are androgen target cells and respond to androgens by the rapid activation of cell signaling. The activation of the PI3K/Akt pathway by 3α‐diol may regulate various properties of astrocytes, including cell motility and survival, and may play a role in the formation and maintenance of the reactive phenotype of ONH astrocytes in glaucoma.
Targeted Versus Daily Naltrexone: Secondary Analysis of Effects on Average Daily Drinking
Authors: Hernandez‐Avila Carlos A. , Song Changhong , Kuo Lynn , Tennen Howard , Armeli Stephen , Kranzler Henry R.
Published: April 2006

Background:To extend our previous findings that naltrexone reduced the likelihood of heavy drinking on a given day among problem drinkers, while targeted administration reduced the likelihood of any drinking, we examined the effects of naltrexone and targeted administration on the continuous outcome of drinks/day. Because treatment response may differ by gender, we also compared the effects on this factor.

Methods:In a double‐blind, placebo‐controlled study, problem drinkers (n=150, 58% men) were randomly assigned to 8 weeks of treatment with naltrexone (50 mg/day) or placebo, either daily or on a targeted schedule. All subjects also received brief coping skills therapy. To complement the traditional regression analysis conducted previously, a zero‐inflated Poisson regression model was used to examine the effects of medication, schedule of administration, and gender on the number of standard drinks consumed daily.

Results:Targeted naltrexone, and to a lesser extent targeted placebo, yielded a greater reduction in daily drinking than did daily placebo, an effect that did not differ by gender and that was greater than that seen for daily naltrexone treatment. Relative to daily placebo, daily naltrexone reduced the number of drinks/day only among men, at the level of a nonsignificant trend.

Conclusions:Although in both genders, targeted treatments appeared to reduce the volume of drinking, treatment with targeted naltrexone was somewhat better. In contrast, heavy drinking women showed no benefit from daily naltrexone treatment. Further evaluation of the efficacy of targeted treatments and of daily naltrexone and the relationship of these treatments with gender is warranted.
Effect of an In‐Home Occupational and Physical Therapy Intervention on Reducing Mortality in Functionally Vulnerable Older People: Preliminary Findings
Authors: Gitlin Laura N. , Hauck Walter W. , Winter Laraine , Dennis Marie P. , Schulz Richard
Published: April 2006

OBJECTIVES: To evaluate the effect of a multicomponent intervention on mortality and the role of control‐oriented strategy use as the change mechanism.

DESIGN: Two‐group randomized design with survivorship followed for 14 months. Participants were randomized to intervention or a no‐treatment control group.

SETTING: Urban, community‐living older people.

PARTICIPANTS: Three hundred nineteen people aged 70 and older with functional difficulties.

INTERVENTION: Occupational therapy and physical therapy sessions involving home modifications, problem solving, and training in energy conservation, safe performance, balance, muscle strength, and fall recovery techniques.

MEASUREMENTS: Survival time was number of days between baseline interview and date of death or final interview if date unknown. Control‐oriented strategy use was measured using eight items.

RESULTS: Intervention participants exhibited a 1% rate of mortality, compared with a 10% rate for no‐treatment control participants (P=.003, 95% confidence interval=2.4–15.04%). At baseline, those who subsequently died had more days hospitalized and lower control‐oriented strategy use 6 months before study enrollment than survivors. No intervention participants with previous days hospitalized (n=31) died, whereas 21% of control group counterparts did (n=35; P=.001). Although intervention participants with low and high baseline control strategy use had lower mortality risk than control participants, mortality risk was lower for intervention participants with low strategy use at baseline (P=.007).

CONCLUSION: An occupational and physical therapy intervention to ameliorate functional difficulties may reduce mortality risk in community‐dwelling older people overall and benefit those most compromised. Instruction in control‐oriented strategies may account for the intervention's protective effects on survivorship.
Computerized Prescribing Alerts and Group Academic Detailing to Reduce the Use of Potentially Inappropriate Medications in Older People
Authors: Simon Steven R. , Smith David H. , Feldstein Adrianne C. , Perrin Nancy , Yang Xiuhai , Zhou Yvonne , Platt Richard , Soumerai Stephen B.
Published: April 2006

OBJECTIVES: To examine the effect of replacing drug‐specific computerized prescribing alerts with age‐specific alerts on rates of dispensing potentially inappropriate medications in older people and to determine whether group academic detailing enhances the effectiveness of these alerts.

DESIGN: Cluster‐randomized trial of group academic detailing and interrupted time‐series analysis.

SETTING: Fifteen clinics of a staff‐model health maintenance organization.

PARTICIPANTS: Seven practices (113 clinicians, 24,119 patients) were randomly assigned to receive age‐specific prescribing alerts plus the academic detailing intervention; eight practices (126 clinicians, 26,805 patients) received alerts alone. Prior implementation of drug‐specific alerts established a downward trend in use of target medications that served as the baseline trend for the present study.

INTERVENTION: The computerized age‐specific alerts occurred at the time of prescribing a targeted potentially inappropriate medication (e.g., tertiary tricyclic amine antidepressants, long‐acting benzodiazepines, propoxyphene) and suggested an alternative medication. Clinicians at seven sites were randomized to group academic detailing, an interactive educational program delivering evidence‐based information.

MEASUREMENTS: Number of target medications dispensed per 10,000 patients per quarter, 2 years before and 1.5 years after the replacement of drug‐specific with age‐specific alerts.

RESULTS: Age‐specific alerts resulted in a continuation of the effects of the drug‐specific alerts without measurable additional effect (P=.75 for level change), but the age‐specific alerts led to fewer false‐positive alerts for clinicians. Group academic detailing did not enhance the effect of the alerts.

CONCLUSION: Age‐specific alerts sustained the effectiveness of drug‐specific alerts to reduce potentially inappropriate prescribing in older people and resulted in a considerably decreased burden of the alerts.
Impaired Executive Function Is Associated with Delirium After Coronary Artery Bypass Graft Surgery
Authors: Rudolph James L. , Jones Richard N. , Grande Laura J. , Milberg William P. , King Emily G. , Lipsitz Lewis A. , Levkoff Sue E. , Marcantonio Edward R.
Published: April 2006

OBJECTIVES: To determine the extent to which preoperative performance on tests of executive function and memory was associated with delirium after coronary artery bypass graft (CABG) surgery.

DESIGN: Prospective observational cohort study.

SETTING: Two academic medical centers and one Department of Veterans Affairs medical center in Massachusetts.

PARTICIPANTS: Eighty subjects without preoperative delirium undergoing CABG or CABG‐valve surgery completed baseline neuropsychological assessments with validated measures of memory and executive function.

MEASUREMENTS: Beginning on postoperative Day 2, a battery to diagnose delirium was administered daily. Confirmatory factor analysis (CFA) was used to define two cognitive domain composites (memory and executive function). The loading pattern of neuropsychological measures onto the latent cognitive domains was determined a priori. Poisson regression was used to model the association between neuropsychological performance and cognitive domain composite scores and risk of postoperative delirium. The association was expressed as the difference between impaired (0.5 standard deviations (SDs) below mean) and nonimpaired (0.5 SDs above mean) performers.

RESULTS: Forty subjects (50%) developed delirium. Measures of memory function were not significantly related to delirium. Of the executive function measures, verbal fluency, category fluency, Hopkins Verbal Learning Test learning, and backward recounting of days and months were significantly related to delirium. Preoperative mental status was a strong predictor of postoperative delirium. After controlling for age, sex, education, medical comorbidity, mental status, and the other cognitive domain, CFA cognitive domain composites suggest that risk for delirium is specific for executive functioning impairment (relative risk (RR) = 2.77, 95% confidence interval (CI) = 1.12–6.87) but not for memory impairment (RR = 0.49, 95% CI = 0.19–1.25).

CONCLUSION: Worse preoperative performance in executive function was independently associated with greater risk of developing delirium after CABG.
Variable Selection for Logistic Regression Using a Prediction‐Focused Information Criterion
Authors: Claeskens Gerda , Croux Christophe , Van Kerckhoven Johan
Published: April 2006

Summary In biostatistical practice, it is common to use information criteria as a guide for model selection. We propose new versions of the focused information criterion (FIC) for variable selection in logistic regression. The FIC gives, depending on the quantity to be estimated, possibly different sets of selected variables. The standard version of the FIC measures the mean squared error of the estimator of the quantity of interest in the selected model. In this article, we propose more general versions of the FIC, allowing other risk measures such as the one based on Lp error. When prediction of an event is important, as is often the case in medical applications, we construct an FIC using the error rate as a natural risk measure. The advantages of using an information criterion which depends on both the quantity of interest and the selected risk measure are illustrated by means of a simulation study and application to a study on diabetic retinopathy.