bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory disease in Niemann‐Pick type C2 is caused by pulmonary alveolar proteinosis
Authors: Griese M , Brasch F , Aldana VR , Cabrera MM , Goelnitz U , Ikonen E , Karam BJ , Liebisch G , Linder MD , Lohse P , Meyer W , Schmitz G , Pamir A , Ripper J , Rolfs A , Schams A , Lezana FJ
Published: December 2009

Griese M, Brasch F, Aldana VR, Cabrera MM, Goelnitz U, Ikonen E, Karam BJ, Liebisch G, Linder MD, Lohse P, Meyer W, Schmitz G, Pamir A, Ripper J, Rolfs A, Schams A, Lezana FJ. Respiratory disease in Niemann‐Pick type C2 is caused by pulmonary alveolar proteinosis.

Niemann‐Pick diseases are hereditary neurovisceral lysosomal lipid storage disorders, of which the rare type C2 almost uniformly presents with respiratory distress in early infancy. In the patient presented here, the NPC2 exon 4 frameshift mutation c.408_409delAA caused reduced NPC2 protein levels in serum and lung lavage fluid and the synthesis of an aberrant, larger sized protein of around 28 kDa. Protein expression was strongly reduced also in alveolar macrophages. The infant developed failure to thrive and tachypnea. Lung lavage, computer tomography, and histology showed typical signs of pulmonary alveolar proteinosis with an abnormal intraalveolar accumulation of surfactant as well as macrophages. An NPC2‐hypomorph animal model also showed pulmonary alveolar proteinosis and accumulation of macrophages in the lung, liver, and spleen long before the mice died. Due to the elevation of cholesterol, the surfactant had an abnormal composition and function. Despite the removal of large amounts of surfactant from the lungs by therapeutic lung lavages, this treatment was only temporarily successful and the infant died of respiratory failure. Our data indicate that respiratory distress in NPC2 disease is associated with a loss of normal NPC2 protein expression in alveolar macrophages and the accumulation of functionally inactive surfactant rich in cholesterol.
Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development
Authors: Moslehi R , Signore C , Tamura D , Mills JL , DiGiovanna JJ , Tucker MA , Troendle J , Ueda T , Boyle J , Khan SG , Oh K‐S , Goldstein AM , Kraemer KH
Published: December 2009

Moslehi R, Signore C, Tamura D, Mills JL, DiGiovanna JJ, Tucker MA, Troendle J, Ueda T, Boyle J, Khan SG, Oh K‐S, Goldstein AM, Kraemer KH. Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development.

The effects of DNA repair and transcription gene abnormalities in human pre‐natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10−6) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD‐affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD‐affected pregnancies. Small for gestational age (SGA) <10th percentile [Relative risk (RR ) = 9.3, 95% CI = 1.4–60.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.1–48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4–29.5, p = 0.02) occurred more frequently among TTD‐affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD‐affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6–92.5, p = 0.0002), elevated mid‐trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0–16.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.4–21.1, p < 0.0001), pre‐term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.9–21.6, p < 0.0001), pre‐eclampsia (RR = 4.0, 95% CI = 1.6–7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6–5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development.
The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation
Authors: Toso Christian , Patel Seema , Asthana Sonal , Kawahara Toshiyasu , Girgis Safwat , Kneteman Norman N. , Shapiro A.M. James , Bigam David L.
Published: December 2009

Toso C, Patel S, Asthana S, Kawahara T, Girgis S, Kneteman NN, Shapiro AMJ, Bigam DL. The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01159.x © 2009 John Wiley & Sons A/S.

Abstract: Background:  There is a lack of data on the use of sirolimus after partial liver transplantation, especially regarding its impact on post‐transplant regeneration.

Methods:  We reviewed adult living donor transplantations, with de novo sirolimus (n = 7) and without sirolimus (n = 21). Liver biopsies were stained for KI‐67, a proliferation marker. Controls included specimens with normal liver parenchyma (n = 13).

Results:  Both groups had similar demographics, graft and patient survival and complication rates. During the first six wk and over the whole first year post‐transplant, the use of sirolimus was associated with lower levels of hepatocyte proliferation compared to sirolimus‐free patients, (overall, 0.3 [0–7.2] vs. 3 [0–49] KI‐67 positive hepatocytes per high power field, p ≤ 0.05). The levels observed in the sirolimus group were similar to those seen in non‐transplanted control patients with normal parenchyma (0.2 [0–1.3], p = NS). Post‐transplant hepatocyte proliferation correlated with the serum levels of sirolimus (p ≤ 0.05), but not with those of tacrolimus or with the dose of mycophenolate mofetil (p = 0.9 and 0.3, respectively).

Conclusions:  These data suggest that sirolimus is associated with decreased post‐transplant hepatocyte proliferation. The clinical significance of this observation remains to be fully determined.
Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience
Authors: Ruiz Richard , Jennings Linda W. , Kim Peter , Tomiyama Koji , Chinnakotla Srinath , Fischbach Bernard V. , Goldstein Robert M. , Levy Marlon F. , McKenna Greg J. , Melton Larry B. , Onaca Nicholas , Randall Henry B. , Sanchez Edmund Q. , Susskind Brian M. , Klintmalm Goran B.
Published: December 2009

Ruiz R, Jennings LW, Kim P, Tomiyama K, Chinnakotla S, Fischbach BV, Goldstein RM, Levy MF, McKenna GJ, Melton LB, Onaca N, Randall HB, Sanchez EQ, Susskind BM, Klintmalm GB. Indications for combined liver and kidney transplantation: propositions after a 23‐yr experience.  Clin Transplant 2010: 24: 807–811. © 2009 John Wiley & Sons A/S.

Abstract:  The frequency of combined liver and kidney transplants (CLKT) persists despite the pronounced scarcity of organs. In this review, we sought to ascertain any factors that would reduce the use of these limited commodities. Seventy‐five adult CLKT were performed over a 23‐yr period at our center, 29 (39%) of which occurred during the Model for End‐stage Liver Disease (MELD) era. Overall, patient survival rates were 82%, 73%, and 62% at one, three, and five yr, respectively. There was no difference in patient survival based either on pre‐transplant hemodialysis status or by glomerular filtration rate (GFR) at the time of transplant. Patients undergoing a second CLKT or a liver retransplantation at the time of CLKT had a survival rate of 30% at three months. In the MELD era, patient survival was unchanged (p = NS) despite an older recipient population (p = 0.0029) and a greater number of hepatitis C patients (p = 0.0428). In summary, patients requiring liver retransplantation with concomitant renal failure should be denied CLKT. Renal allografts may also be spared by implementing strict criteria for renal organ allocation (GFR < 30 mL/min at the time of evaluation) and considering the elimination of preemptive kidney transplantation in CLKT.
Reactive oxygen species and nitric oxide in plant mitochondria: origin and redundant regulatory systems
Authors: Blokhina Olga , Fagerstedt Kurt V.
Published: December 2009

Plant mitochondria differ from their mammalian counterparts in many respects, which are due to the unique and variable surroundings of plant mitochondria. In green leaves, plant mitochondria are surrounded by ample respiratory substrates and abundant molecular oxygen, both resulting from active photosynthesis, while in roots and bulky rhizomes and fruit carbohydrates may be plenty, whereas oxygen levels are falling. Several enzymatic complexes in mitochondrial electron transport chain (ETC) are capable of reactive oxygen species (ROS) formation under physiological and pathological conditions. Inherently connected parameters such as the redox state of electron carriers in the ETC, ATP synthase activity and inner mitochondrial membrane potential, when affected by external stimuli, can give rise to ROS formation via complexes I and III, and by reverse electron transport (RET) from complex II. Superoxide radicals produced are quickly scavenged by superoxide dismutase (MnSOD), and the resulting H2O2 is detoxified by peroxiredoxin–thioredoxin system or by the enzymes of ascorbate–glutathione cycle, found in the mitochondrial matrix. Arginine‐dependent nitric oxide (NO)‐releasing activity of enzymatic origin has been detected in plant mitochondria. The molecular identity of the enzyme is not clear but the involvement of mitochondria‐localized enzymes responsible for arginine catabolism, arginase and ornithine aminotransferase has been shown in the regulation of NO efflux. Besides direct control by antioxidants, mitochondrial ROS production is tightly controlled by multiple redundant systems affecting inner membrane potential: NAD(P)H‐dependent dehydrogenases, alternative oxidase (AOX), uncoupling proteins, ATP‐sensitive K+ channel and a number of matrix and intermembrane enzymes capable of direct electron donation to ETC. NO removal, on the other hand, takes place either by reactions with molecular oxygen or superoxide resulting in peroxynitrite, nitrite or nitrate ions or through interaction with non‐symbiotic hemoglobins or glutathione. Mitochondrial ROS and NO production is tightly controlled by multiple redundant systems providing the regulatory mechanism for redox homeostasis and specific ROS/NO signaling.
Effect of Organic Selenium in the Diet on Sperm Quality of Boars
Authors: López A , Rijsselaere T , Van Soom A , Leroy JLMR , De Clercq JBP , Bols PEJ , Maes D
Published: December 2009

Contents

The effect of a diet supplemented with organic selenium (Se) on sperm production and quality of boars was investigated. Sixty mature boars from a commercial artificial insemination centre were randomly allocated at Day (D) 0 into Group A and B. Group A received the regular ration supplemented with inorganic Se (0.4 mg/kg feed as Na2SeO3) whereas Group B was switched to the same diet but with organic Se (0.4 mg/kg fed as Se‐yeast). The sperm was investigated during 4 months (D0, D30, D60, D75, D90, D105 and D120). Sperm concentration and motility were objectively measured using a photometer and Computer Assisted Semen Analysis (CASA) respectively. Morphology of the sperm was assessed using eosin–nigrosin staining and the resistance to induction of oxidative stress (production of malonaldehyde, MDA) through thiobarbituric acid reagent species analysis. Additionally, the Se concentration in sperm and blood plasma were measured. Repeated measures analysis of variance (anova) from D60 to 120 (spermatogenesis of approximately 2 months) or anova at D120 (Se concentrations) were used for statistical analysis. The total number of ejaculated sperm was not significantly different between both groups, but boars of Group B had a significantly higher sperm concentration (434.6 vs 514.1 × 106 sperm/ml; p < 0.05). Small differences (p < 0.05) were observed between both groups for some CASA parameters, namely straight line velocity (μm/s) (Group A: 48.3, Group B: 45.1), straightness (%) (Group A: 65.6, Group B: 62.2) and linearity (%) (Group A: 32.2, Group B: 29.3). The sperm of Group B showed more oxidative stress (4.1 vs 4.9 μmol MDA/l; p < 0.05) compared with those of Group A. No significant differences (p > 0.05) were observed for the other parameters. Under the present study conditions, changing from inorganic Se to organic Se in the diet of boars increased sperm concentration but reduced some motility parameters and resistance to oxidative stress.
Genetics of basal cell carcinoma
Authors: De Zwaan Sally E , Haass Nikolas K
Published: December 2009

Basal cell carcinoma is the most common human malignancy in populations of European origin, and Australia has the highest incidence of basal cell carcinoma in the world. Great advances in the understanding of the genetics of this cancer have occurred in recent years. Mutations of the patched 1 gene (PTCH1) lead to basal cell carcinoma predisposition in Gorlin syndrome. PTCH1 is part of the hedgehog signalling pathway, and derangements within this pathway are now known to be important in the carcinogenesis of many different cancers including sporadic basal cell carcinoma. The molecular biology of the hedgehog pathway is discussed, and mouse models of basal cell carcinoma based on this pathway are explored. New developments in non‐surgical treatment of basal cell carcinoma are based on this knowledge. Other genes of importance to basal cell carcinoma development include the tumour suppressor gene P53 and the melanocortin‐1 receptor gene. In addition, we discuss molecules of possible importance such as the glutathione‐S‐transferases, DNA repair genes, cyclin‐dependent kinase inhibitor 2A, Brahma and connexins. Evidence of familial aggregation of this cancer is explored and supports the possibility of genetic predisposition to this common malignancy.
Facial transplantation as an option in reconstructive surgery: no mountains too high?
Authors: Błogowski Wojciech
Published: December 2009

Background: Human facial allotransplantation (FA) is a testament to the impressive progress, which was and is still happening in the field of transplantation medicine and reconstructive surgery. Like every pioneering treatment option, FA faces both the clinicians' and public opinion with a huge amount of medical and psychosocial dilemmas, which, in order to introduce FA as a scientifically and socially accepted procedure into clinical practice, need to be discussed, answered and solved.

Methods: This review is based on a detailed literature research in all relevant databases (MEDLINE, PubMed, Cochrane Library, specialist textbooks), however, recent papers (published between 2006 and 2008) were given highest priority for inclusion.

Results: In this review, two main limitations associated with facial tissue allotransplantation, that is, shortage of donations and life‐long need for immunosuppressive treatment, are discussed and presented in both psychosocial and medical terms.

Conclusion: Although both of these limitations potentially could successfully inhibit the transformation of FA from an experimental therapy to the treatment of choice for patients with severe functional facial impairment, recent literature suggest that FA will find a meaningful place in facial reconstructive surgery.
Art of preserving health: studies on the medical supervision of physical exercise
Authors: Thurston Alan J.
Published: December 2009

To the ancient Greeks, physical exercise was an essential part of life, especially during adolescence and young adulthood. Long after the end of the Classical Greek era, Roman conquest brought a shift towards martial training, increased professionalism in athletic competition and a weak strand of restorative gymnastics kept barely intact by the likes of Galen. While the crux of these teachings was the use of exercise, among other things, to promote and maintain health, the emphasis began to shift to concerns about the health of athletes and the medical problems brought about by exercise. Fashions in athletic training began to change in the mid‐nineteenth century, but the mystique associated with athletic training pervaded much of the thinking and still persists today where, in this modern scientific period of exercise and health, physiologists, physical educators and physicians have become involved in seeking to apply the scientific method to what has become known as exercise science. The modern concept of sports medicine tends to emphasize the training and welfare of the elite athlete.
Supplementary motor area and anterior intraparietal area integrate fine‐graded timing and force control during precision grip
Authors: Haller Sven , Chapuis Dominique , Gassert Roger , Burdet Etienne , Klarhöfer Markus
Published: December 2009

We investigated the neuronal processing of the physiologically particularly important precision grip (opposition of index finger and thumb) by the combination of functional magnetic resonance imaging (fMRI) and an MR‐compatible haptic interface. Ten healthy subjects performed isometric precision grip force generation with visual task instruction and real‐time visual feedback in a block design. In a 2 × 2 two‐factorial design, both the timing and force could be either constant or varying (identical average timing and force). As we expected only small changes in the fMRI response for the different fine‐graded motor control conditions, we maximized the sensitivity of the data analysis and implemented a volumes of interest (VOI) restricted general linear model analysis including non‐explanatory force regressors to eliminate directly force‐related low‐level activations. The VOIs were defined based on previous studies. We found significant associations: timing variation (variable vs. constant) and primary motor area (M1) and dorsal premotor area (PMd); force variation (variable vs. constant) and primary somatosensory area (S1), anterior intraparietal area (AIP) and PMd; interaction of timing and force and supplementary motor area (SMA) and AIP. We conclude that SMA and AIP integrate fine‐graded higher‐level timing and force control during precision grip. M1, S1 and PMd process lower‐level timing and force control, yet not their integration. These results are the basis for a detailed assessment of manual motor control in a variety of motor diseases. The detailed behavioural assessment by our MR‐compatible haptic interface is particularly valuable in patients due to expected larger inter‐individual variation in motor performance.
β‐Secretase‐1 elevation in transgenic mouse models of Alzheimer’s disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development
Authors: Zhang Xue‐Mei , Cai Yan , Xiong Kun , Cai Huaibin , Luo Xue‐Gang , Feng Jia‐Chun , Clough Richard W. , Struble Robert G. , Patrylo Peter R. , Yan Xiao‐Xin
Published: December 2009

The presence of neuritic plaques is a pathological hallmark of Alzheimer’s disease (AD). However, the origin of extracellular β‐amyloid peptide (Aβ) deposits and the process of plaque development remain poorly understood. The present study attempted to explore plaque pathogenesis by localizing β‐secretase‐1 (BACE1) elevation relative to Aβ accumulation and synaptic/neuritic alterations in the forebrain, using transgenic mice harboring familial AD (FAD) mutations (5XFAD and 2XFAD) as models. In animals with fully developed plaque pathology, locally elevated BACE1 immunoreactivity (IR) coexisted with compact‐like Aβ deposition, with BACE1 IR occurring selectively in dystrophic axons of various neuronal phenotypes or origins (GABAergic, glutamatergic, cholinergic or catecholaminergic). Prior to plaque onset, localized BACE1/Aβ IR occurred at swollen presynaptic terminals and fine axonal processes. These BACE1/Aβ‐containing axonal elements appeared to undergo a continuing process of sprouting/swelling and dystrophy, during which extracellular Aβ IR emerged and accumulated in surrounding extracellular space. These data suggest that BACE1 elevation and associated Aβ overproduction inside the sprouting/dystrophic axonal terminals coincide with the onset and accumulation of extracellular amyloid deposition during the development of neuritic plaques in transgenic models of AD. Our findings appear to be in harmony with an early hypothesis that axonal pathogenesis plays a key or leading role in plaque formation.
Sensorimotor training promotes functional recovery and somatosensory cortical map reactivation following cervical spinal cord injury
Authors: Martinez Marina , Brezun Jean‐Michel , Zennou‐Azogui Yoh’i , Baril Nathalie , Xerri Christian
Published: December 2009

Sensorimotor activity has been shown to play a key role in functional recovery after partial spinal cord injury (SCI). Most studies in rodents have focused on the rehabilitation of hindlimb locomotor functions after thoracic or lumbar SCI, whereas forelimb motor and somatosensory abilities after cervical SCI remain largely uninvestigated, despite the high incidence of such injuries in humans. Moreover, little is known about the neurophysiological substrates of training‐induced recovery in supraspinal structures. This study was aimed at evaluating the effects of a training procedure combining both motor and sensory stimulation on behavioral performance and somatosensory cortical map remodeling after cervical (C4–C5) spinal hemisection in rats. This SCI severely impaired both sensory and motor capacities in the ipsilateral limbs. Without training, post‐lesion motor capacities gradually improved, whereas forepaw tactile abilities remained impaired. Consistently, no stimulus‐evoked responses were recorded within the forepaw representational zone in the primary somatosensory (S1) cortex at 2 months after the SCI. However, our data reveal that with training started from the 7th day post‐lesion, a nearly complete recovery (characterized by an early and rapid improvement of motor functions) was associated with a gradual compensation of tactile deficits. Furthermore, the recovery of tactile abilities was correlated with the areal extent of reactivation of S1 cortex forepaw representations. Rehabilitative training promoted post‐lesion adaptive plasticity, probably by enhancing endogenous activity within spared spinal and supraspinal circuits and pathways sustaining sensory and motor functions. This study highlights the beneficial effect of sensorimotor training in motor improvement and its critical influence on tactile recovery after SCI.
Deletion of Cav2.1(α1A) subunit of Ca2+‐channels impairs synaptic GABA and glutamate release in the mouse cerebellar cortex in cultured slices
Authors: Lonchamp Etienne , Dupont Jean‐Luc , Doussau Frédéric , Shin Hee‐Sup , Poulain Bernard , Bossu Jean‐Louis
Published: December 2009

Deletion of both alleles of the P/Q‐type Ca2+‐channel Cav2.1(α1A) subunit gene in mouse leads to severe ataxia and early death. Using cerebellar slices obtained from 10 to 15 postnatal days mice and cultured for at least 3 weeks in vitro, we have analysed the synaptic alterations produced by genetically ablating the P/Q‐type Ca2+‐channels, and compared them with the effect of pharmacological inhibition of the P/Q‐ or N‐type channels on wild‐type littermate mice. Analysis of spontaneous synaptic currents recorded in Purkinje cells (PCs) indicated that the P/Q‐type channels play a prominent role at the inhibitory synapses afferent onto the PCs, with the effect of deleting Cav2.1(α1A) partially compensated. At the granule cell (GC) to PC synapses, both N‐ and P/Q‐type Ca2+‐channels were found playing a role in glutamate exocytosis, but with no significant phenotypic compensation of the Cav2.1(α1A) deletion. We also found that the P/Q‐ but not N‐type Ca2+‐channel is indispensable at the autaptic contacts between PCs. Tuning of the GC activity implicates both synaptic and sustained extrasynaptic γ‐aminobutyric acid (GABA) release, only the former was greatly impaired in the absence of P/Q‐type Ca2+‐channels. Overall, our data demonstrate that both P/Q‐ and N‐type Ca2+‐channels play a role in glutamate release, while the P/Q‐type is essential in GABA exocytosis in the cerebellum. Contrary to the other regions of the CNS, the effect of deleting the Cav2.1(α1A) subunit is partially or not compensated at the inhibitory synapses. This may explain why cerebellar ataxia is observed at the mice lacking functional P/Q‐type channels.
Motor foundations of higher cognition: similarities and differences in processing regular and violated perceptual sequences of different specificity
Authors: Bubic Andreja , Yves von Cramon D. , Schubotz Ricarda I.
Published: December 2009

Processing perceptual sequences relies on the motor system, which is able to simulate the dynamics of the environment by developing internal representations of external events and using them to predict the incoming stimuli. Although it has previously been demonstrated that such models may incorporate predictions based on exact stimulus properties and single stimulus dimensions, it is not known whether they can also support abstract predictions pertaining to the level of stimulus categories. This issue was investigated within the present event‐related functional magnetic resonance imaging study, which compared the processing of perceptual sequences of different specificity, namely those in which the sequential structure was based on the order of presentation of individual stimuli (token), and those in which such structure was defined by stimulus categories (type). The results obtained indicate a comparable engagement of the basic premotor–parietal network in processing both specific and categorical perceptual sequences. However, type sequences additionally elicited activations within the lateral prefrontal, occipital and posterior temporal regions that supported categorization in this task context. Introducing sequential deviants into token sequences activated parietotemporal and ventrolateral frontal cortices, whereas a less pronounced overall response, dominated by lateral prefrontal activation, was elicited by violations introduced into type sequences. Overall, the findings obtained suggest that, although forward models in perception may be able to incorporate expectations of lower specificity when compared to the motor domain, such processing is crucially dependent on additional contributions from lateral prefrontal as well as inferior occipital and temporal cortices that support categorization occurring in such a dynamic context.
Temporal characteristics of global motion processing revealed by transcranial magnetic stimulation
Authors: Stevens Laura K. , McGraw Paul V. , Ledgeway Tim , Schluppeck Denis
Published: December 2009

The ability to detect the motion of objects is critical to survival, and understanding the cortical mechanisms involved in this process remains a key challenge in sensory neuroscience. A relatively new approach to this problem is to temporarily disrupt processing at specific cortical sites and measure the behavioural consequences. Several previous studies have shown that transcranial magnetic stimulation (TMS) of human visual area V5/MT disrupts global motion perception, but reports vary widely in the timescale of this effect. To resolve this issue we employed psychophysical techniques to investigate how discrimination of translational, rotational and radial global motion is affected by TMS. Prior to applying TMS we established baseline coherence thresholds for global motion perception. Adopting each observer’s coherence level at threshold we examined how TMS delivered to V5/MT modulated performance. Importantly, we measured the influence of single‐pulse TMS over a broad temporal range to reveal the fine temporal structure of the disruption profile for global motion perception. Results show that the disruption profile consisted of two distinct epochs during which global direction judgments were reliably impaired, separated by an interval in which performance was unaffected. The bimodal nature of the distribution profiles is consistent with feedforward and feedback processing between visual areas mediating global motion processing. We present a novel quantitative model that characterizes the contribution of each process to visual motion perception.
Evaluation of JPEG and JPEG2000 compression algorithms for dermatological images
Authors: Gulkesen KH , Akman A , Yuce YK , Yilmaz E , Samur AA , Isleyen F , Cakcak DS , Alpsoy E
Published: December 2009

Background  Some image compression methods are used to reduce the disc space needed for the image to store and transmit the image efficiently. JPEG is the most frequently used algorithm of compression in medical systems. JPEG compression can be performed at various qualities. There are many other compression algorithms; among these, JPEG2000 is an appropriate candidate to be used in future.

Objective  To investigate perceived image quality of JPEG and JPEG2000 in 1 : 20, 1 : 30, 1 : 40 and 1 : 50 compression rates.

Methods  In total, photographs of 90 patients were taken in dermatology outpatient clinics. For each patient, a set which is composed of eight compressed images and one uncompressed image has been prepared. Images were shown to dermatologists on two separate 17‐inch LCD monitors at the same time, with one as compressed image and the other as uncompressed image. Each dermatologist evaluated 720 image couples in total and defined whether there existed any difference between two images in terms of quality. If there was a difference, they reported the better one. Among four dermatologists, each evaluated 720 image couples in total.

Results  Quality rates for JPEG compressions 1 : 20, 1 : 30, 1 : 40 and 1 : 50 were 69%, 35%, 10% and 5% respectively. Quality rates for corresponding JPEG2000 compressions were 77%, 67%, 56% and 53% respectively.

Conclusion  When JPEG and JPEG2000 algorithms were compared, it was observed that JPEG2000 algorithm was more successful than JPEG for all compression rates. However, loss of image quality is recognizable in some of images in all compression rates.
Political Myth, Mythology and the European Union*
Authors: DELLA SALA VINCENT
Published: December 2009

The EU, as is commonly held, is a different form of political rule: a polity based on rationality and functional interests, not emotional appeals. Without reference to the narrative of the nation or the state, the question emerges as to whether the European Union needs or has myths? If it does, what are they and how successful have they been? The aim of this article – indeed of the special issue – is to explore the role of political myth in creating normative and cognitive foundations for governing in the EU and to examine whether these are applicable to the case of the European Union.
Temporal requirements of insulin/IGF‐1 signaling for proteotoxicity protection
Authors: Cohen Ehud , Du Deguo , Joyce Derek , Kapernick Erik A. , Volovik Yuli , Kelly Jeffery W. , Dillin Andrew
Published: December 2009

Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late‐onset human neurodegenerative disorders. Reduction of insulin/IGF‐1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer’s disease‐linked Aβ peptide. We utilized transgenic nematodes that express human Aβ and found that late life IIS reduction efficiently protects from Aβ toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)‐1 to modulate a protein disaggregase, while DAF‐16 regulates a presumptive active aggregase, raising the question of how these opposing activities could be co‐regulated. One possibility is that HSF‐1 and DAF‐16 have distinct temporal requirements for protection from proteotoxicity. Using a conditional RNAi approach, we found an early requirement for HSF‐1 that is distinct from the adult functions of DAF‐16 for protection from proteotoxicity. Our data also indicate that late life IIS reduction can protect from proteotoxicity when it can no longer promote longevity, strengthening the prospect that IIS reduction might be a promising strategy for the treatment of neurodegenerative disorders caused by proteotoxicity.
Using Scanner Technology to Collect Expenditure Data*
Authors: Leicester Andrew , Oldfield Zoë
Published: December 2009

In terms of collecting panel expenditure data, there are trade‐offs between the demands imposed on respondents and the detail and coverage of data collected. Comprehensive spending data tend to be cross‐sectional whilst panel studies include only limited, aggregated expenditure questions. Recently, economists have begun to use detailed, bar‐code‐level spending data from household panels collected by market research companies. However, there has not been a detailed assessment of the strengths and weaknesses of this collection method or its implications for the recorded data. This paper seeks to fill this gap by providing an in‐depth examination of data from one company, Taylor Nelson Sofres (TNS), recording grocery purchases over five years. We assess how far the ongoing demands of participation lead to ‘fatigue’ in respondents' recording of their spending and the implications for household attrition, and we provide a detailed comparison of the expenditure data collected by TNS and the well‐established Expenditure and Food Survey (EFS). Broadly, we suggest that problems of fatigue and attrition may not be particularly severe, though there are differences in expenditures that cannot be attributed to demographic or time effects and may be suggestive of survey mode effects.
Experimental Tests of Survey Responses to Expenditure Questions*
Authors: Comerford David , Delaney Liam , Harmon Colm
Published: December 2009

This paper tests for a number of survey effects in the elicitation of expenditure items. In particular, we examine the extent to which individuals use features of the expenditure question to construct their answers. We test whether respondents interpret question wording as researchers intend and examine the extent to which prompts, clarifications and seemingly arbitrary features of survey design influence expenditure reports. We find that over one‐quarter of respondents have difficulty distinguishing between ‘you’ and ‘your household’ when making expenditure reports; that respondents report higher pro‐rata expenditure when asked to give responses on a weekly as opposed to annual timescale; that respondents give higher estimates when using a scale with a higher midpoint; and that respondents report higher aggregated expenditure when categories are presented in a disaggregated form. In summary, expenditure reports are constructed using convenient rules of thumb and available information, which will depend on the characteristics of the respondent, the expenditure domain and features of the survey question. It is crucial to further account for these features in ongoing surveys.
Mechanism of the anti‐obesity effects induced by a novel Melanin‐concentrating hormone 1‐receptor antagonist in mice
Authors: Ito Masahiko , Ishihara A , Gomori A , Matsushita H , Ito Makoto , Metzger JM , Marsh DJ , Haga Y , Iwaasa H , Tokita S , Takenaga N , Sato N , MacNeil DJ , Moriya M , Kanatani A
Published: December 2009

Background and purpose:  Melanin‐concentrating hormone (MCH) is an orexigenic neuropeptide expressed in the lateral hypothalamus that is involved in feeding and body weight regulation. Intracerebroventricular infusion of a peptidic MCH1 receptor antagonist ameliorated obesity in murine models. Recently, small molecule MCH1 receptor antagonists have been developed and characterized for the treatment of obesity. However, little is known of the mechanism of the anti‐obesity effects of MCH1 receptor antagonists.

Experimental approach:  To examine the mechanisms of action of the anti‐obesity effect of MCH1 receptor antagonists more precisely, we conducted a pair‐feeding study in mice with diet‐induced obesity (DIO), chronically treated with an orally active and highly selective MCH1 receptor antagonist and examined changes in mRNA expression levels in liver, brown and white adipose tissues. We also assessed the acute effects of the MCH1 receptor antagonist in energy expenditure under thermoneutral conditions.

Key results:  Treatment with the MCH1 receptor antagonist at 30 mg·kg−1 for 1 month moderately suppressed feeding and significantly reduced body weight by 24%. In contrast, pair‐feeding resulted in a smaller weight reduction of 10%. Treatment with the MCH1 receptor antagonist resulted in a higher body temperature compared with the pair‐fed group. TaqMan and calorimetry data suggested that the MCH1 receptor antagonist also stimulated thermogenesis.

Conclusions and implications:  Our results indicate that an MCH1 receptor antagonist caused anti‐obesity effects im mice by acting on both energy intake and energy expenditure.
Functional characterization of nonsynonymous single nucleotide polymorphisms in the human organic anion transporter 4 (hOAT4)
Authors: Zhou Fanfan , Zhu Ling , Cui Pei H. , Church W. Bret , Murray Michael
Published: December 2009

Background and purpose: The human organic anion transporter (hOAT) family of transmembrane carrier proteins mediate the cellular flux of anionic substances, including certain hormones and anti‐cancer drugs. hOAT4 is highly expressed at the apical membrane of the renal tubular cell and facilitates drug re‐absorption in the kidney. In the present study, the impact of 10 nonsynonymous single nucleotide polymorphisms (SNPs) of hOAT4 on transport function in COS‐7 cells was characterized.

Experimental approach: Transport uptake assay was used to assess the function of the variant transporters. Cell surface biotinylation and western blot analysis were used to investigate the expression characteristics of the transporter proteins. Comparative modelling was used to interpret the influence of nonsynonymous changes in terms of hOAT4 structure.

Key results: Four naturally occurring hOAT4 variants (L29P, R48Y, V155G and T392I) exhibited a significant loss of function. Substitution of leucine‐29, which is a conserved residue in OATs, with a proline residue, impaired the synthesis or the apparent stability of the transporter and membrane insertion was disrupted in the R48Y variant. In the case of the V155G and T392I variants, impaired function was due to decreased affinity of the transporter for oestrone sulphate and impaired transporter‐substrate turnover respectively. The T392I variant was inhibited more extensively than the wild‐type transporter by the cationic substrate tetraethyl ammonium.

Conclusions and implications: Several naturally occurring SNPs encode variant hOAT4s that may impair the renal tubular re‐absorption of important drug substrates.
Proposed Definition of Environmental Damage Illustrated by the Cases of Genetically Modified Crops and Invasive Species
Authors: BARTZ ROBERT , HEINK ULRICH , KOWARIK INGO
Published: December 2009

Abstract:  The introduction of non‐native plant species and the release of genetically modified (GM) crops can induce environmental changes at gene to ecosystem levels. Regulatory frameworks such as the Convention on Biological Diversity or the EU Deliberate Release Directive aim to prevent environmental damage but do not define the term. Although ecologists and conservationists often refer to environmental effects of GM crops or invasive species as damage, most authors do not disclose their normative assumptions or explain why some environmental impacts are regarded as detrimental and others are not. Thus far, a concise definition of environmental damage is missing and is necessary for a transparent assessment of environmental effects or risks. Therefore, we suggest defining environmental damage as a significant adverse effect on a biotic or abiotic conservation resource (i.e., a biotic or abiotic natural resource that is protected by conservational or environmental legislation) that has an impact on the value of the conservation resource, the conservation resource as an ecosystem component, or the sustainable use of the conservation resource. This definition relies on three normative assumptions: only concrete effects on a conservation resource can be damages; only adverse effects that lead to a decrease in the value of the conservation resource can be damages; and only significant adverse effects constitute damage to a conservation resource. Applying this definition within the framework of environmental risk assessment requires further normative determinations, for example, selection of a threshold to distinguish between adverse and significant adverse effects and approaches for assessing the environmental value of conservation resources. Such determinations, however, are not part of the definition of environmental damage. Rather they are part of the definition's operationalization through assessment procedures, which must be grounded in a comprehensible definition of environmental damage.
Haloperidol Prophylaxis for Elderly Hip‐Surgery Patients at Risk for Delirium: A Randomized Placebo‐Controlled Study
Authors: Kalisvaart Kees J. , De Jonghe Jos F. M. , Bogaards Marja J. , Vreeswijk Ralph , Egberts Toine C. G. , Burger Bart J. , Eikelenboom Piet , Van Gool Willem A.
Published: December 2009

Objectives:To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip‐surgery patients at risk for delirium.

Design:Randomized, double‐blind, placebo‐controlled trial.

Setting:Large medical school–affiliated general hospital in Alkmaar, the Netherlands.

Participants:A total of 430 hip‐surgery patients aged 70 and older at risk for postoperative delirium.

Intervention:Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients.

Measurements:The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version‐98 (DRS‐R‐98)), the duration of delirium, and the length of hospital stay.

Results:The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6–1.3); the mean highest DRS‐R‐98 score±standard deviation was 14.4±3.4 and 18.4±4.3, respectively (mean difference 4.0, 95% CI=2.0–5.8;P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0–8.0;P<.001); and the mean number of days in the hospital was 17.1±11.1 and 22.6±16.7, respectively (mean difference 5.5 days, 95% CI=1.4–2.3;P<.001). No haloperidol‐related side effects were noted.

Conclusion:Low‐dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.
Relationship Between Serum Insulin‐Like Growth Factor‐1 Levels and Alzheimer's Disease and Vascular Dementia
Authors: Watanabe Takuya , Miyazaki Akira , Katagiri Takashi , Yamamoto Hideki , Idei Tsunenori , Iguchi Takashi
Published: December 2009

Objectives: To determine whether decreased serum insulin‐like growth factor‐1 (IGF‐1) levels could be a risk factor for dementia in older people.

Design: Case control study.

Setting: Showa University Karasuyama Hospital, Tokyo, Japan.

Participants: A total of 436 Japanese elderly subjects: 106 patients with Alzheimer's disease (AD), 103 patients with vascular dementia (VaD), and 227 age‐matched controls without dementia.

Mesurements: Serum concentrations of IGF‐1 and atherogenic lipoproteins, carotid artery intima‐media thickness (IMT), and plaques were determined.

Results: Mini‐Mental State Examination (MMSE) scores were positively correlated with serum IGF‐1 concentrations as well as mean blood pressure or body mass index and were negatively correlated with age, serum low‐density lipoprotein cholesterol and lipoprotein(a) concentrations, and carotid IMT. Serum IGF‐1 concentrations had a significant inverse correlation with carotid IMT. Analysis across the IGF‐1 quartiles revealed a threshold effect of low IGF‐1 on MMSE score in subjects with the IGF‐1 levels of 140 ng/mL or less (50% percentile) versus those with IGF‐1 levels greater than 140 ng/mL. Multiple logistic regression concerning AD and VaD retained serum IGF‐1 concentrations of 140 ng/mL or less and carotid IMT of 0.9 mm or more. Patients with AD and VaD had significantly lower IGF‐1 concentrations and greater mean IMT than nondemented controls.

Conclusion: These results suggest that decreased serum IGF‐1 level and the progression of carotid atherosclerosis could play a role as independent risk factors for dementia.
Intraindividual Variability and the Effect of Acute Illness on Immune Senescence Markers
Authors: High Kevin P. , Trader Melissa , Pahor Marco , Loeb Mark
Published: December 2009

Objectives: To determine the intraindividual variability and effect of acute illness on two markers of immune senescence.

Design: Cohort study with repeated measures.

Setting: Clinical research center and emergency department at two academic medical centers.

Participants: Seventy‐three subjects aged 65 and older enrolled in three groups: chronic underlying conditions but no acute illness, acutely ill with infection (community‐acquired pneumonia), and acutely ill without infection.

Measurements: CD16 density on polymorphonuclear neutrophils (PMNs) and the proportion of CD8+ T cells that express CD28 determined twice in the nonacutely ill group and three times (Days 0, 30, and 60) in the acute illness groups.

Results: In the nonacutely ill group, PMN CD16 density demonstrated wide intraindividual variation, but there was a strong correlation for repeated measures of the percentage of CD8+ T cells expressing CD28 (correlation coefficient (r)=0.77, P<.001). Acute illness markedly affected both measures, regardless of whether the illness was due to infection; there was no correlation between measures obtained on Day 0 versus Day 30 for either immune marker. In contrast, a strong correlation existed between Day 30 and Day 60 values, particularly for CD8+/CD28+ percentage (r=0.58–0.86; P=.006 to <.001).

Conclusion: The percentage of CD8+ T cells that express CD28 is a highly reproducible marker of immune senescence. Although acute illness affects this marker, 30 to 60 days of convalescence appears adequate for it to return to baseline.