bluuebunny/crossref_metadata_2025 huggingface dataset:
Eye Movements of the Murine P/Q Calcium Channel Mutant Tottering, and the Impact of Aging
Authors: Stahl John S. , James Robert A. , Oommen Brian S. , Hoebeek Freek E. , De Zeeuw Chris I.
Published: December 2005

Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains.
Expression and Function of Variants of Slob, Slowpoke Channel Binding Protein, inDrosophila
Authors: Jaramillo Angela M. , Zeng Haoyu , Fei Hong , Zhou Yi , Levitan Irwin B.
Published: December 2005

Slob binds to and modulates the Drosophila Slowpoke (dSlo) calcium-activated potassium channel and also recruits the ubiquitous signaling protein 14-3-3 to the channel regulatory complex. RT-PCR reveals the presence of multiple slob transcripts in Drosophila heads. The transcripts are predicted to encode proteins that we call Slob51 (kDa), Slob57, Slob65, and Slob71. Slob51 and Slob65 are splice variants that lack a motif important for the binding of 14-3-3. Previous microarray analyses demonstrated the circadian cycling of slob mRNA, and we show by quantitative PCR that more than one transcript cycles in fly heads. Using in situ hybridization, we observe differences in the expression patterns of the different transcripts. Immunohistochemistry on Drosophila heads reveals Slob71/65 protein to be enriched in the lateral neurons, in contrast to Slob57/51 protein, which is expressed most prominently in the pars intercerebralis neurons and dorsal giant interneurons. Using a heterologous expression system, we show that different Slobs bind to different extents to dSlo and 14-3-3. These data reveal an unexpected diversity of the dSlo/Slob/14-3-3 dynamic regulatory complex.
Neural Correlates of Attention and Distractibility in the Lateral Intraparietal Area
Authors: Bisley James W. , Goldberg Michael E.
Published: December 2005

We examined the activity of neurons in the lateral intraparietal area (LIP) during a task in which we measured attention in the monkey, using an advantage in contrast sensitivity as our definition of attention. The animals planned a memory-guided saccade but made or canceled it depending on the orientation of a briefly flashed probe stimulus. We measured the monkeys' contrast sensitivity by varying the contrast of the probe. Both subjects had better thresholds at the goal of the saccade than elsewhere. If a task-irrelevant distractor flashed elsewhere in the visual field, the attentional advantage transiently shifted to that site. The population response in LIP correlated with the allocation of attention; the attentional advantage lay at the location in the visual field whose representation in LIP had the greatest activity when the probe appeared. During a brief period in which there were two equally active regions in LIP, there was no attentional advantage at either location. This time, the crossing point, differed in the two animals, proving a strong correlation between the activity and behavior. The crossing point of each neuron depended on the relationship of three parameters: the visual response to the distractor, the saccade-related delay activity, and the rate of decay of the transient response to the distractor. Thus the time at which attention lingers on a distractor is set by the mechanism underlying these three biophysical properties. Finally, we showed that for a brief time LIP neurons showed a stronger response to signal canceling the planned saccade than to the confirmation signal.
Texture Signals in Whisker Vibrations
Authors: Hipp Joerg , Arabzadeh Ehsan , Zorzin Erik , Conradt Jorg , Kayser Christoph , Diamond Mathew E. , König Peter
Published: December 2005

Rodents excel in making texture judgments by sweeping their whiskers across a surface. Here we aimed to identify the signals present in whisker vibrations that give rise to such fine sensory discriminations. First, we used sensors to capture vibration signals in metal whiskers during active whisking of an artificial system and in natural whiskers during whisking of rats in vivo. Then we developed a classification algorithm that successfully matched the vibration frequency spectra of single trials to the texture that induced it. For artificial whiskers, the algorithm correctly identified one texture of eight alternatives on 40% of trials; for in vivo natural whiskers, the algorithm correctly identified one texture of five alternatives on 80% of trials. Finally, we asked which were the key discriminative features of the vibration spectra. Under both artificial and natural conditions, the combination of two features accounted for most of the information: The modulation power—the power of the part of the whisker movement representing the modulation due to the texture surface—increased with the coarseness of the texture; the modulation centroid—a measure related to the center of gravity within the power spectrum—decreased with the coarseness of the texture. Indeed, restricting the signal to these two parameters led to performance three-fourths as high as the full spectra. Because earlier work showed that modulation power and centroid are directly related to neuronal responses in the whisker pathway, we conclude that the biological system optimally extracts vibration features to permit texture classification.
Interactions Between Asynchronous Release and Short-Term Plasticity in the Nucleus Accumbens Slice
Authors: Hjelmstad Gregory O.
Published: December 2005

Glutamate synapses in the nucleus accumbens (NAc) display asynchronous release in response to trains of stimulation. However, it is unclear what role this asynchronous release plays in synaptic transmission in this nucleus. This process was studied, specifically looking at the interaction between short-term depression and asynchronous release. These results indicate that synchronous and asynchronous release do not compete for a depleted readily releasable pool of vesicles.
Engineering Myocardial Tissue
Authors: Eschenhagen Thomas , Zimmermann Wolfram H.
Published: December 2005

To create an artificial heart is one of the most ambitious dreams of the young field of tissue engineering, a dream that, when publicly announced in 1999 (LIFE initiative around M. Sefton), provoked as much compassion as scepticism in the scientific and lay press. Today, it is fair to state that the field is still far away from having built the “bioartificial heart.” Nevertheless, substantial progress has been made over the past 10 years, and a realistic perspective exists to create 3-dimensional heart muscle equivalents that may not only serve as experimental models but could also be useful for cardiac regeneration.
Predictors of Long-Term Mortality in Patients With Ischemic Stroke Referred for Transesophageal Echocardiography
Authors: Ward R. Parker , Don Creighton W. , Furlong Kathy T. , Lang Roberto M.
Published: December 2005

Background and Purpose—

Findings on transesophageal echocardiography (TEE) after ischemic stroke predict recurrent embolic events and prompt therapy; however, the additive predictive power of TEE findings on long-term mortality is unknown. Our goal was to study the impact of TEE findings on all cause mortality in ischemic stroke patients referred for TEE.

Methods—

We reviewed 245 consecutive patients who underwent TEE for ischemic stroke of undetermined origin (2000 to 2003). Long-term survival was assessed using the Social Security Death Index.

Results—

In a mean follow-up period of 3.0 (1.4 to 4.8) years, death occurred in 19.2% of patients. TEE findings included patent foramen ovale (18.8%), left atrium/left ventricle thrombus (2.4%), spontaneous echo contrast (3.7%), atrial septal aneurysm (3.3%), valve vegetation/mass/tumor (7.8%), complex aortic atheroma ([CAA]; 14.7%), and the composite of any cardiac source of embolus (39.2%). A total atherosclerotic burden (TAB) score was also recorded. On Cox hazard regression analysis, measures of aortic atherosclerosis (CAA [hazard ratio (HR), 2.7; 95% CI, 1.4 to 5.3] or TAB score [HR, 1.4; 95% CI, 1.2 to 1.6]) were independent predictors of death, whereas other TEE findings were not.

Conclusion—

In patients with ischemic stroke of undetermined origin referred for TEE, measures of aortic atherosclerosis, including CAA, represent the only TEE findings that predict long-term mortality after all other clinical factors are considered. Further study is needed to determine whether treatments for CAA effect long-term survival in patients with ischemic stroke.
The Use of Image Exchange in Examining Relationship Role Perceptions
Authors: Eckstein Daniel , Clemmer Fern , Fierro Armando
Published: December 2005

This article explores partnership role discrepancies as perceived by couples. Image exchange highlights the benefits of mutually shared role perceptions and normative expectations of marital partners. Relevant theory and practice recommendations are offered.
Toward a normative theory of normative marketing theory
Authors: Wilkinson Ian F. , Young Louise C.
Published: December 2005

We show how different approaches to developing marketing strategies depend on the type of environment a firm faces, where environments are distinguished in terms of their systems properties rather than their content. Particular emphasis is given to turbulent environments in which outcomes are not a priori predictable and are not traceable to individual firm actions and we show that, in these conditions, the relevant unit of competitive response and understanding is no longer the individual firm but the network of relations comprising interdependent, interacting firms. Networks of relations are complex adaptive systems that are more ‘intelligent’ than the individual firms that comprise them and are capable of comprehending and responding to more complex and turbulent environments. Yet they are co-produced by the patterns of actions and interactions of the firms involved. The creation and accessing of such distributed intelligence cannot be centrally directed, as this necessarily limits it. Instead managers and firms are involved in a kind of participatory planning and adaptation process through which the network self-organizes and adapts. Drawing on research in systems theory, complexity, biology and cognitive science, extensions to the resource-based theory of the firm are proposed that include how resources are linked across relations and networks in a dynamic and evolutionary way. The concepts of an extended firm and soft-assembled strategies are introduced to describe the nature of the strategy development process. This results in a more theoretically grounded basis for understanding the nature and role of relationship and network strategies in marketing and management. We finish by considering the research implications of our analysis and the role of agent-based models as a means of sensitizing and informing management action.
Framing marketing effectiveness as a process and outcome
Authors: Kahn Kenneth B. , Myers Matthew B.
Published: December 2005

Marketing effectiveness is a fundamental performance dimension of the marketing organization, traditionally viewed as an output variable predicated on goal attainment. Recent literature, however, has portrayed a broader conceptualization of effectiveness that disputes this strict goal attainment model. The present article builds on this recent work by contending that marketing effectiveness should be viewed as a process and an outcome to mitigate the challenges that arise when a marketing organization solely ascribes to a goal perspective. We proffer a marketing effectiveness framework to outline implications and spur future research on marketing performance control.
Gaming for Beginners
Authors: Miller Toby
Published: December 2005

This article examines the history of moral panics about media, gleans some lessons from media studies that can help the study of electronic games, and is critical of both utopic and dystopic, cybertarian and pessimistic accounts of gaming.
Game Studies Now, History of Science Then
Authors: Lowood Henry
Published: December 2005

This article compares the growth of history of science as a discipline to the situation faced by game studies today. What can researchers learn from the elevation of the history of science to an established discipline and profession that might help scholars understand the situation of game studies? And why are game studies today being talked about in ways similar to the rhetoric that accompanied the history of science in the 1960s and 1970s? The author suggests that the growth of history of science then and game studies now has been fueled by similar motivations and strategies. These reflections on the history of science suggest there is nothing about such divisions that dooms or even threatens the growth and eventual success of this new discipline.
Law and Games Studies
Authors: Lastowka Greg
Published: December 2005

This brief article investigates the relationship between legal scholarship and game studies. It attempts to find some common ground between theories of law and theories of games, looking to lawas a game, the lawof sports, and contemporary claims about online governance.
Why Game Studies Now? Gamers Don't Bowl Alone
Authors: Williams Dmitri
Published: December 2005

Researchers are encouraged to study the social uses and effects of gaming before stereotypes form and guide both their own and the public's thinking. The rise of online games comes at a particular historical moment for social reasons as well as technological ones and prompts a wide array of questions. The transition of public life from common spaces to private ones is exemplified in the move of game play from arcades to homes. As our real-world civic and social institutions experience steady decay, what is the impact of transferring our social networks and communities into virtual spaces? Will games become our new third places, and how will that affect us? These are questions researchers can answer but ones that need to be addressed before ideologues, defenders, and attackers muddle empiricism.
Signs, Symbols, Games, and Play
Authors: Myers David
Published: December 2005

This article justifies the study of video games with reference to the importance of the study of representations and the study of play.
Why Game Studies Now? Video Games: A New Art Form
Authors: Gee James Paul
Published: December 2005

Video games are a new art form, and this, the author argues, is one good reason why now is the right time for game studies. As a new art form, one largely immune to traditional tools developed for the analysis of literature and film, video games will challenge researchers to develop new analytical tools and will become a new type of “equipment for living,” to use Kenneth Burke's phrase for the role of literature. This article discusses several of the features that make video games a unique art form, features that will, the author believes, come to play a role in analyses of games in the emerging field of game studies.
The Question of Computer Games
Authors: Crogan Patrick
Published: December 2005

A short, speculative account of the state of play in the formation of a discipline or field of computer games studies. The processes of academic teaching, research, and institutional positioning in regard to computer games are viewed from the perspective of wider currents and crises influencing knowledge formation today. It is argued that the different approaches to computer games cannot ignore the differences in their conceptions of the object of study in a naive pluralism. These different conceptions of games as parts of the technocultural milieu must encounter each other in the name of the struggle against the avoidance of critical thought concerning the nature and forms of technoculture that often prevails in the production of specialist “knowledge” today.
Armageddon Army
Authors: Haynes Cynthia
Published: December 2005

Scholars are witnessing a dramatic confluence of faith, politics, and gaming. On the stage of this war theater, the players are indistinguishable, the simulations just one mission removed from real war. One is immersed in war as game, the other in war as eternal battle. The military has invested millions in developing games as strategic communications tools, hiring real soldiers and officers as consultants to ensure optimal realism in game play. Nowthat the harmonic convergence of faith, politics, and computer games has been graphically (and brutally) realized, specifically, made real in the dueling holy wars— ours and theirs (jihad)—what now? This article proposes a game modification of the god mode of the game, America’s Army, as a critical response to the reality ofwar and the use of computer games as military recruitment tools.
A Moment in the Life of a Generation (Why Game Studies Now?)
Authors: Mäyrä Frans
Published: December 2005

Game studies entering academia means that games are finally positioned at the heart of a dedicated field of learning. There is a tension however as the need and demand for game studies has faced the opposing, structural forces that slowdown the development. It is hard to ignore the cultural significance of digital games and play, particularly as numerous game play experiences underlie personal relations and histories within an ICT-Penetrated society. Rather than a single “game culture,” there are several of them, as visible and invisible sense-making structures that surface not only in games themselves, but in the language, practices, and sensibilities adopted and developed by groups and individuals. As the academia is loaded with expectations of providing games industry with workforce or opportunities for more innovative and experimental game culture, it is good to remember that the fundamental task of universities is to create knowledge and promote learning.
Patriarchy, Crime, and Justice
Authors: Chesney-Lind Meda
Published: December 2005

Feminist criminology, as an outgrowth of the second wave of feminism, came of age during a period of considerable change and political optimism. As a mature field, it now inhabits a social and political landscape radically altered and increasingly characterized by the politics of backlash. Given feminist criminology’s dual focus on gender and crime, it is uniquely positioned to respond to two core aspects of the current backlash political agenda: racism and sexism. To do this effectively, feminist criminology must prioritize research on the race/gender/punishment nexus. This article provides three examples of how such a focus exposes the crucial roles played by constructions of the crime problem as well as current crime-control strategies in the ratification and enforcement of antifeminist and racist agendas. Finally, the field must seek creative ways to blend scholarship with activism while simultaneously providing support and encouragement to emerging feminist criminologists willing to take such risks.
The Gendered Nature of Risk Factors for Delinquency
Authors: Belknap Joanne , Holsinger Kristi
Published: December 2005

Traditional delinquency theories typically exclude girls and examine economic marginalization as the primary risk factor for boys. More recent mainstream theories expand the childhood strains associated with delinquency but fail to account for the link between childhood abuses and subsequent offending reported in the feminist pathways studies of girls and women. In addition, policies since the 1990s request the development of “gender-specific services” for delinquent girls without examining how the risks are gendered. This study of 444 incarcerated youths’ self-reports indicates the contribution of feminist pathways to better understand the risks associated with and improve the responses to girls’ and boys’ delinquency by examining demographic, abuse, family, school and peer, and self-esteem variables.
Gender Gap Trends for Violent Crimes, 1980 to 2003
Authors: Steffensmeier Darrell , Zhong Hua , Ackerman Jeff , Schwartz Jennifer , Agha Suzanne
Published: December 2005

The authors examine 1980 to 2003 trends in female-to-male interpersonal violence reported in Uniform Crime Reports (UCR) arrest statistics and National Crime Victimization Survey (NCVS) victimization data. Augmented Dickey-Fuller time-series techniques and intuitive plot displays show much overlap yet differences in each source’s portrayal of trends in female violence levels and the gender gap. Both sources show little or no change in the gender gap for homicide and rape/sexual assault, whereas UCR police counts show a sharp rise in female-to-male arrests for criminal assault during the past one to two decades—but that rise is not borne out in NCVS counts. Net-widening policy shifts have apparently escalated the arrest proneness of females for “criminal assault” (e.g., policing physical attacks/threats of marginal seriousness that women in relative terms are more likely to commit); rather than women having become any more violent, official data increasingly mask differences in violent offending by men and women.
Biphasic effect of extracellular ATP on human and rat airways is due to multiple P2 purinoceptor activation
Authors: Mounkaïla Boutchi , Marthan Roger , Roux Etienne
Published: December 2005

Background

Extracellular ATP may modulate airway responsiveness. Studies on ATP-induced contraction and [Ca2+]isignalling in airway smooth muscle are rather controversial and discrepancies exist regarding both ATP effects and signalling pathways. We compared the effect of extracellular ATP on rat trachea and extrapulmonary bronchi (EPB) and both human and rat intrapulmonary bronchi (IPB), and investigated the implicated signalling pathways.

Methods

Isometric contraction was measured on rat trachea, EPB and IPB isolated rings and human IPB isolated rings. [Ca2+]iwas monitored fluorimetrically using indo 1 in freshly isolated and cultured tracheal myocytes. Statistical comparisons were done with ANOVA or Student'sttests for quantitative variables and χ2tests for qualitative variables. Results were considered significant at P < 0.05.

Results

In rat airways, extracellular ATP (10-6–10-3M) induced an epithelium-independent and concentration-dependent contraction, which amplitude increased from trachea to IPB. The response was transient and returned to baseline within minutes. Similar responses were obtained with the non-hydrolysable ATP analogous ATP-γ-S. Successive stimulations at 15 min-intervals decreased the contractile response. In human IPB, the contraction was similar to that of rat IPB but the time needed for the return to baseline was longer. In isolated myocytes, ATP induced a concentration-dependent [Ca2+]iresponse. The contractile response was not reduced by thapsigargin and RB2, a P2Y receptor inhibitor, except in rat and human IPB. By contrast, removal of external Ca2+, external Na+and treatment with D600 decreased the ATP-induced response. The contraction induced by α-β-methylene ATP, a P2X agonist, was similar to that induced by ATP, except in IPB where it was lower. Indomethacin and H-89, a PKA inhibitor, delayed the return to baseline in extrapulmonary airways.

Conclusion

Extracellular ATP induces a transient contractile response in human and rat airways, mainly due to P2X receptors and extracellular Ca2+influx in addition with, in IPB, P2Y receptors stimulation and Ca2+release from intracellular Ca2+stores. Extracellular Ca2+influx occurs through L-type voltage-dependent channels activated by external Na+entrance through P2X receptors. The transience of the response cannot be attributed to ATP degradation but to purinoceptor desensitization and, in extrapulmonary airways, prostaglandin-dependent PKA activation.
Comparative analysis of programmed cell death pathways in filamentous fungi
Authors: Fedorova Natalie D , Badger Jonathan H , Robson Geoff D , Wortman Jennifer R , Nierman William C
Published: December 2005

Background

Fungi can undergo autophagic- or apoptotic-type programmed cell death (PCD) on exposure to antifungal agents, developmental signals, and stress factors. Filamentous fungi can also exhibit a form of cell death called heterokaryon incompatibility (HI) triggered by fusion between two genetically incompatible individuals. With the availability of recently sequenced genomes of Aspergillus fumigatus and several related species, we were able to define putative components of fungi-specific death pathways and the ancestral core apoptotic machinery shared by all fungi and metazoa.

Results

Phylogenetic profiling of HI-associated proteins from four Aspergilli and seven other fungal species revealed lineage-specific protein families, orphan genes, and core genes conserved across all fungi and metazoa. The Aspergilli-specific domain architectures include NACHT family NTPases, which may function as key integrators of stress and nutrient availability signals. They are often found fused to putative effector domains such as Pfs, SesB/LipA, and a newly identified domain, HET-s/LopB. Many putative HI inducers and mediators are specific to filamentous fungi and not found in unicellular yeasts. In addition to their role in HI, several of them appear to be involved in regulation of cell cycle, development and sexual differentiation. Finally, the Aspergilli possess many putative downstream components of the mammalian apoptotic machinery including several proteins not found in the model yeast, Saccharomyces cerevisiae.

Conclusion

Our analysis identified more than 100 putative PCD associated genes in the Aspergilli, which may help expand the range of currently available treatments for aspergillosis and other invasive fungal diseases. The list includes species-specific protein families as well as conserved core components of the ancestral PCD machinery shared by fungi and metazoa.
Bacterial isolates from blood cultures of children with suspected septicaemia in Calabar, Nigeria
Authors: Meremikwu Martin M , Nwachukwu Chukwuemeka E , Asuquo Anne E , Okebe Joseph U , Utsalo Simon J
Published: December 2005

Background

Septicaemia is a common cause of morbidity and mortality among children in the developing world. This pattern has changed little in the past decade. Physical signs and symptoms, though useful in identifying possible cases have limited specificity. Definitive diagnosis is by bacteriologic culture of blood samples to identify organisms and establish antibiotic susceptibility. These results are usually not available promptly. Therefore a knowledge of epidemiologic and antimicribial susceptibility pattern of common pathogens is useful for prompt treatment of patients. This report highlights the pattern of bacterial isolates in our environment from a retrospective study of our patients' records.

Methods

One thousand, two hundred and one blood samples were analysed from children aged 0–15 years, admitted into the children's wards of the University of Calabar Teaching Hospital, Calabar, Nigeria with features suggesting septicaemia. Samples were collected under aseptic conditions and cultured for aerobic and anaerobic organisms. Isolates were identified using bacteriologic and biochemical methods and antibiotic sensitivity determined by agar diffusion method using standard antibiotic discs.

Results

Bacteria was isolated in 552 (48.9%) of samples with highest rates among newborns (271 : 50.8). The most frequent isolates were Staphylococcal aureus (48.7%) and Coliforms (23.4%). Results showed high susceptibilities to the Cephalosporins (Ceftriazone- 100%:83.2%, Cefuroxime-100%:76.5%) and Macrolides (Azithromycin-100%:92.9%) for S. aureus and coliforms respectively. This study underscores the importance of septicaemia as a common cause of febrile illness in children and provides information on common prevalent aetiologic agents and drug susceptibilities of the commonest pathogens.

Conclusion

Staphylococcus aureus and coliforms were the leading causes of septicaemia in children in this locality, and the third generation cephalosporins and azithromycin were shown to be effective against these pathogens.
Mandibular facial talon cusp: Case report
Authors: Oredugba Folakemi A
Published: December 2005

Background

Talon cusp is a supernumerary structure projecting from the dento-enamel junction to a variable distance towards the incisal edge of an anterior tooth. Studies have shown that it consists of enamel, dentine and a variable amount of pulp tissue. Hyperactivity of the enamel organ during morphodifferentiation has been attributed to its formation. Most previous reports have been made concerning the occurrence of this structure on primary and permanent teeth and mostly on the palatal aspect. Only few have been reported on the facial aspect of the teeth. When it occurs, the effects are mainly aesthetic and functional and so early detection and treatment is essential in its management to avoid complications.

Case presentation

An unusual case of talon cusp on the facial aspect of a mandibular central incisor is reported. Its presence resulted in attrition of the opposing tooth. Reduction of the cusp and topical application of fluoride gel was initiated.

Conclusion

The management and treatment outcome of talon cusp depends on the size, presenting complications and patient cooperation.
Epidemiology of forest malaria in central Vietnam: a large scale cross-sectional survey
Authors: Erhart Annette , Thang Ngo Duc , Van Ky Phan , Tinh Ta Thi , Van Overmeir Chantal , Speybroeck Niko , Obsomer Valerie , Hung Le Xuan , Thuan Le Khanh , Coosemans Marc , D'alessandro Umberto
Published: December 2005

In Vietnam, a large proportion of all malaria cases and deaths occurs in the central mountainous and forested part of the country. Indeed, forest malaria, despite intensive control activities, is still a major problem which raises several questions about its dynamics.

A large-scale malaria morbidity survey to measure malaria endemicity and identify important risk factors was carried out in 43 villages situated in a forested area of Ninh Thuan province, south central Vietnam. Four thousand three hundred and six randomly selected individuals, aged 10–60 years, participated in the survey. Rag Lays (86%), traditionally living in the forest and practising "slash and burn" cultivation represented the most common ethnic group. The overall parasite rate was 13.3% (range [0–42.3] whilePlasmodium falciparumseroprevalence was 25.5% (range [2.1–75.6]). Mapping of these two variables showed a patchy distribution, suggesting that risk factors other than remoteness and forest proximity modulated the human-vector interactions. This was confirmed by the results of the multivariate-adjusted analysis, showing that forest work was a significant risk factor for malaria infection, further increased by staying in the forest overnight (OR= 2.86; 95%CI [1.62; 5.07]). Rag Lays had a higher risk of malaria infection, which inversely related to education level and socio-economic status. Women were less at risk than men (OR = 0.71; 95%CI [0.59; 0.86]), a possible consequence of different behaviour. This study confirms that malaria endemicity is still relatively high in this area and that the dynamics of transmission is constantly modulated by the behaviour of both humans and vectors. A well-targeted intervention reducing the "vector/forest worker" interaction, based on long-lasting insecticidal material, could be appropriate in this environment.
Anticoagulant treatment at a specialized outpatient anticoagulant therapy unit, a descriptive study
Authors: Ekblom Kim , Hultdin Johan , Carlberg Bo , Strand Tage
Published: December 2005

Background

The indications for continuous oral anticoagulant treatment, the target interval and the procedures for withdrawing treatment have changed in the last 10 years.

Methods

Patients on continuous oral anticoagulant treatment at the Outpatient Anticoagulant Clinic at Umeå University Hospital in 2002 were included in a descriptive study (n = 900). 263 of those had a mechanical heart valve prosthesis. Only patient records for patients with other indications than mechanical heart valve prosthesis were examined. 582 of those records were found. In the 55 remaining patients some clinical information was retrieved from the computerised warfarin dosage database. These latter, more unsure clinical data, are presented separately. Anticoagulant treatment was discontinued if lack of proper indication or presence of too high risk for hemorrhagic complications were found.

Results

The prevalence of continuous oral anticoagulant treatment in the uptake area was 0.65%. The most common target interval was INR 2.1–3.0, but patients with a mechanical heart valve prosthesis were often treated more aggressively, i.e. with a higher INR target interval. Of the patients on continuous treatment, 26.6% of the INR values were outside 2.0–3.0. The most common reasons for oral anticoagulant treatment were atrial fibrillation or mechanical heart valve prosthesis, in contrast to earlier findings in studies of our population in 1987 and 1990. We found 90 patients (10.0%) without proper indication for oral anticoagulant treatment or too high risk, and their treatment was discontinued.

Conclusion

In patients on oral anticoagulant therapy, re-evaluation of indications and risks resulted in a substantial number of treatment withdrawals. There have been major changes in treatment indications during the last decade, possibly due to rapid development of knowledge in the field of thrombosis risk factors. Treatment should be re-considered once a year.
Community pharmacy services to optimise the use of medications for mental illness: a systematic review
Authors: Bell Simon , McLachlan Andrew J , Aslani Parisa , Whitehead Paula , Chen Timothy F
Published: December 2005

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder
Fishers' knowledge and seahorse conservation in Brazil
Authors: Rosa Ierecê ML , Alves Rômulo RN , Bonifácio Kallyne M , Mourão José S , Osório Frederico M , Oliveira Tacyana PR , Nottingham Mara C
Published: December 2005

From a conservationist perspective, seahorses are threatened fishes. Concomitantly, from a socioeconomic perspective, they represent a source of income to many fishing communities in developing countries. An integration between these two views requires, among other things, the recognition that seahorse fishers have knowledge and abilities that can assist the implementation of conservation strategies and of management plans for seahorses and their habitats. This paper documents the knowledge held by Brazilian fishers on the biology and ecology of the longsnout seahorse Hippocampus reidi. Its aims were to explore collaborative approaches to seahorse conservation and management in Brazil; to assess fishers' perception of seahorse biology and ecology, in the context evaluating potential management options; to increase fishers' involvement with seahorse conservation in Brazil. Data were obtained through questionnaires and interviews made during field surveys conducted in fishing villages located in the States of Piauí, Ceará, Paraíba, Maranhão, Pernambuco and Pará. We consider the following aspects as positive for the conservation of seahorses and their habitats in Brazil: fishers were willing to dialogue with researchers; although captures and/or trade of brooding seahorses occurred, most interviewees recognized the importance of reproduction to the maintenance of seahorses in the wild (and therefore of their source of income), and expressed concern over population declines; fishers associated the presence of a ventral pouch with reproduction in seahorses (regardless of them knowing which sex bears the pouch), and this may facilitate the construction of collaborative management options designed to eliminate captures of brooding specimens; fishers recognized microhabitats of importance to the maintenance of seahorse wild populations; fishers who kept seahorses in captivity tended to recognize the condtions as poor, and as being a cause of seahorse mortality.
Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy
Authors: Munzone Elisabetta , Curigliano Giuseppe , Rocca Andrea , Bonizzi Giuseppina , Renne Giuseppe , Goldhirsch Aron , Nolè Franco
Published: December 2005

Introduction

The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer.

Methods

Ten patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER or PgR, were treated with weekly trastuzumab at standard doses with or without chemotherapy.

Results

Three out of 10 patients showed overexpression of ERs first appearing after 9, 12 and 37 weeks, respectively, from the initiation of trastuzumab. Two of these patients were subsequently treated with endocrine therapy alone: one of them received letrozole for 3 years without evidence of progression.

Conclusion

Therapeutic targets enabling the appearance of an endocrine responsive disease may increase treatment options for patients with breast cancer. Furthermore, these clinical data suggest that an ER-negative phenotype is a multi-step process with a reversible repression modality, and that some ER-negative tumors may either revert to an ER-positive phenotype, allowing an endocrine treatment to be effective.
α‐Thalassemia: Hb H Disease and Hb Barts Hydrops Fetalis
Authors: CHUI DAVID H.K.
Published: December 2005

Abstract: α‐Thalassemia mutations are one of the most common mutations of man, and they cause Hb H disease and Hb Barts hydrops fetalis. Hb H disease is not necessarily a benign disorder as has been generally thought. Furthermore, in southern China and in Southeast Asia, there are 2‐3 times more fetuses afflicted with the invariably fatal Hb Barts hydrops fetalis than with the β‐thalassemia major or intermedia. These findings underscore the public health importance of these hereditary disorders, and they call for better education, diagnosis, treatment, prevention, and research for these diseases.
Hemoglobin E‐β‐Thalassemia: Progress Report from the International Study Group
Authors: PREMAWARDHENA ANUJA , DE SILVER SHANTHIMALA , ARAMBEPOLA MAHINDA , OLIVIERI NANCY F. , VICHINSKY ELLIOTT P. , MERSON LAURA , MURACO GIULIA , ALLEN ANGELA , FISHER CHRISTOPHER , PETO TIMOTHY , WEATHERALL DAVID J.
Published: December 2005

Abstract: A long‐term observational study of Hb E‐β‐thalassemia in Sri Lanka is beginning to define some of the genetic and environmental factors that are responsible for its remarkable phenotypic variability. In this population there is a very small difference between the steady‐state hemoglobin levels between the mild and severe phenotypes, and it has been possible to stop transfusion in many of those who have been on long‐term treatment of this kind. These preliminary observations, made over the last 7 years, provide directions for future research into this increasingly important disease.
Survival and Complications in Thalassemia
Authors: BORGNA‐PIGNATTI C. , CAPPELLINI M. D. , DE STEFANO P. , DEL VECCHIO G. C. , FORNI G. L. , GAMBERINI M. R. , GHILARDI R. , ORIGA R. , PIGA A. , ROMEO M. A. , ZHAO H. , CNAAN A.
Published: December 2005

Abstract: The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long‐term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication‐free survival continue to improve, due to better treatment strategies. New complications are appearing in long‐term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.
Understanding α‐Globin Gene Regulation: Aiming to Improve the Management of Thalassemia
Authors: HIGGS D.R. , GARRICK D. , ANGUITA E. , DE GOBBI M. , HUGHES J. , MUERS M. , VERNIMMEN D. , LOWER K. , LAW M. , ARGENTARO A. , DEVILLE M. A. , GIBBONS R.
Published: December 2005

Abstract: Over the past 50 years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the α‐ and β‐globin genes are normally regulated and documenting the effects of inherited mutations that cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans‐acting mutations are being found more often. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression that, in turn, may open up new avenues for improving the management of patients with common types of thalassemia.
Role of Alpha Hemoglobin‐Stabilizing Protein in Normal Erythropoiesis and β‐Thalassemia
Authors: WEISS MITCHELL J. , ZHOU SUIPING , FENG LIANG , GELL DAVID A. , MACKAY JOEL P. , SHI YIGONG , GOW ANDREW J.
Published: December 2005

Abstract: Hemoglobin (Hb) synthesis is coordinated by homeostatic mechanisms to limit the accumulation of free α or β subunits, which are cytotoxic. Alpha hemoglobin‐stabilizing protein (AHSP) is an abundant erythroid protein that specifically binds free αHb, stabilizes its structure, and limits its ability to participate in chemical reactions that generate reactive oxygen species. Gene ablation studies in mice demonstrate that AHSP is required for normal erythropoiesis. AHSP‐null erythrocytes are short‐lived, contain Hb precipitates, and exhibit signs of oxidative damage. Loss of AHSP exacerbates β‐thalassemia in mice, indicating that altered AHSP expression or function could modify thalassemia phenotypes in humans, a topic that is beginning to be explored in clinical studies. We used biochemical, spectroscopic, and crystallographic methods to examine how AHSP stabilizes αHb. AHSP binds the G and H helices of αHb on a surface that largely overlaps with the α1‐β1 interface of HbA. This result explains previous findings that βHb can competitively displace AHSP from αHb to form HbA tetramer. Remarkably, binding of AHSP to oxygenated αHb induces dramatic conformational changes and converts the heme‐bound iron to an oxidized hemichrome state in which all six coordinate positions are occupied. This structure limits the reactivity of heme iron, providing a mechanism by which AHSP stabilizes αHb. These findings suggest a biochemical pathway through which AHSP might participate in normal Hb synthesis and modulate the severity of thalassemias. Moreover, understanding how AHSP stabilizes αHb provides a theoretical basis for new strategies to inhibit the damaging effects of free αHb that accumulates in β‐thalassemia.
Evaluation of ICL670, a Once‐Daily Oral Iron Chelator in a Phase III Clinical Trial of β‐Thalassemia Patients with Transfusional Iron Overload
Authors: GALANELLO RENZO
Published: December 2005

Abstract: Osteoporosis and osteopenia are frequent complications of thalassemia major (TM) and intermedia (TI). Osteoporosis was found in 23/25 patients with TI and in 115/239 patients with TM. In TM, no association was found with specific polymorphisms in candidate genes (vitamin D receptor, estrogen receptor, calcitonin receptor, and collagen type 1 alpha 1). Osteoporosis in TM female was strongly associated with primary amenorrhea (P < .0001), while in male patients with TM hypogonadism was not significantly related to BMD (P= .0001). Low BMD was also associated with cardiomiopathy (P= .01), diabetes mellitus (P= .0001), chronic hepatitis (P= .0029), and increased ALT (P= .01).