The novel 5-lipoxygenase inhibitor ABT-761 attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage

OBJECTIVE: Eicosanoids have been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Leukotrienes, 5-hydroxyperoxyeicosatetraenoic acid, and 5-hydroxyeicosatetraenoic acid are part of this group of substances, resulting from the 5-lipoxygenase activity on arachidonic acid metabolism. This study examined the effects of ABT-761, a new 5-lipoxygenase inhibitor, on cerebral vasospasm in an in vivo rabbit model of SAH. METHODS: A total of 48 rabbits were assigned to one of six groups: SAH + placebo (n = 8), SAH + ABT-761 20 mg/kg (n = 8), SAH + ABT-761 30 mg/kg (n = 8), control + placebo (n = 8), control + ABT-761 20 mg/kg (n = 8), and control + ABT-761 30 mg/kg (n = 8). Drug administration was initiated 30 minutes after induction of SAH and repeated 24 hours later. The animals were killed 48 hours after SAH, using the perfusion-fixation method. The cross sectional areas of basilar artery histological sections were measured by an investigator blinded to the treatment groups of the individual samples. RESULTS: In placebo-treated animals, the average luminal cross sectional area of the basilar artery was reduced by 68% after SAH as compared with controls (P < 0.0001). After SAH, the vasospastic response was attenuated in animals treated with 20 or 30 mg/kg representing a 28 or 35% reduction, respectively (P = 0.0011 and P = 0.0038). CONCLUSION: The results demonstrated that ABT-761 is effective in attenuating experimental cerebral vasospasm, indicating that this new drug represents a potential therapeutic agent for the treatment of vasospasm after SAH

What is the experience of receiving healthcare for neck pain?

This study used a descriptive phenomenological approach to describe the experience of finding and receiving health services for neck pain. Nineteen participants (18 females, 1 male) with neck pain (>3 months) were interviewed using a semi-structured questionnaire guide. Interviews were recorded, transcribed and coded. Two overarching themes described the experience: complexity in finding effective health care; and the need for informative, personalized, respectful communication. Complexity in finding effective health care was attributed to the variable approach and effectiveness of different health professionals, the need to experiment with care to find what works, the need to differentiate temporary versus permanent treatment effects, concerns about treatment side effects and the sense that financial factors influence personal treatment choices and provider behaviours. The need for informative, personalized, respectful communications was broken down into the following subthemes: the importance of being listened to, seen and believed; the need for useful information; and a desire to have outcomes formally tracked as a means of individualizing treatment. Overall, patients struggled to navigate the variable health services and providers that were available and that provided variable outcomes. They often did so through a trial and error approach. As such, patients remain open to unproven, even controversial treatment options. Research evidence was not a key ingredient in patient decision-making about accessing health services. The environmental, personal, health behavior factors interacted to contribute to health service utilization and would increase the burden of these for both the individual and society at large. The effectiveness of neck pain interventions is dependent on complex interactions between the context, individual, and health care provider, therefore, physiological responses cannot be considered as being distinct from these determinants

Sperm death and dumping in Drosophila

Mating with more than one male is the norm for females of many species. In addition to generating competition between the ejaculates of different males, multiple mating may allow females to bias sperm use. In Drosophila melanogaster, the last male to inseminate a female sires approximately 80% of subsequent progeny. Both sperm displacement, where resident sperm are removed from storage by the incoming ejaculate of the copulating male, and sperm incapacitation, where incoming seminal fluids supposedly interfere with resident sperm, have been implicated in this pattern of sperm use. But the idea of incapacitation is problematic because there are no known mechanisms by which an individual could damage rival sperm and not their own. Females also influence the process of sperm use, but exactly how is unclear. Here we show that seminal fluids do not kill rival sperm and that any 'incapacitation' is probably due to sperm ageing during sperm storage. We also show that females release stored sperm from the reproductive tract (sperm dumping) after copulation with a second male and that this requires neither incoming sperm nor seminal fluids. Instead, males may cause stored sperm to be dumped or females may differentially eject sperm from the previous mating

The variability of birth weight

The material for this study was obtained from the maternity records relating to single births occurring in Malta throughout 1965. In this year there were 5,719 total births; of these the sample studied covers 2,517 births (44.11 percent). The records were personally examined by one of the authors (Cremona, 1967) from St. Luke's Hospital Malta, from Maltese private Hospitals, and from the District Nursing Association. In Malta the mean birth weight for male babies is 3446g, and for female babies 3358g. The mean birth weight tends to increase with the mother's parity, and this trend continues even with the higher parities. The association between birth weight and rising maternal age remains uncertain. It is also probable that birth weight has a geographical determinant. Birth weight is a multifactorial product and cannot be very reliable as a clinical parameter. A new terminology is necessary to distinguish between three different groups of babies with low birth weights.peer-reviewe

Crédito Rural: Sustentabilidade E O Paradoxo Do Desenvolvimento Econômico Social Do Campo

Considering that rural credit has an important role in the modernization and operation of the field by the promotion of agricultural activities, enabling the countryside social and economic development, the objective by this article, is to demonstrate that the institute in frank evolution of an earlier priority for the operation and modernization of farming techniques and pastoral seeking a higher yield, has gone up over time to have a priority for the sustainability of the field by the creation of aid programs for family agriculture and its foundations.So even if the means are temporally disjointed, it is understood that the objectives of sustainability and social economic development of the field would possess the common goal of benefiting the farmers, however, certainly there would be a paradox between them, since the rural credit is taken as the principal by agricultural expansion in 70s, as well by the fact that Brazil is now a world power in agribusiness, which also encompass the environment degradation that has occurred since then. Considerando que o crédito rural possui um papel relevante na modernização e operacionalização do campo mediante o fomento das atividades agropecuárias, possibilitando o desenvolvimento econômico social da zona rural, objetiva-se pelo presente artigo, demonstrar que o instituto em franca evolução, de uma anterior primazia pela operacionalização e modernização das técnicas de exploração agrícola e pastoril, visando um maior rendimento, passa-se com o tempo a se ter uma primazia pela sustentabilidade do campo ante a criação dos programas de auxílio a agricultura familiar e seus fundamentos. Assim, mesmo que temporalmente desconexos, entende-se que os objetivos da sustentabilidade e do desenvolvimento econômico social do campo possuiriam o objetivo comum de beneficiar o produtor rural. Entretanto, tem-se que haveria um paradoxo entre ambos, já que o crédito rural é tomado como o principal responsável pela expansão agrícola na década de 70, bem como pelo fato do Brasil ser hoje uma potência mundial no agronegócio, o que abarcaria também a degradação do meio ambiente ocorrida desde então

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Ice flow dynamics and surface meltwater flux at a land-terminating sector of the Greenland ice sheet

AbstractWe present satellite-derived velocity patterns for the two contrasting melt seasons of 2009–10 across Russell Glacier catchment, a western, land-terminating sector of the Greenland ice sheet which encompasses the K(angerlussuaq)-transect. Results highlight great spatial heterogeneity in flow, indicating that structural controls such as bedrock geometry govern ice discharge into individual outlet troughs. Results also reveal strong seasonal flow variability extending 57 km up-glacier to 1200 m elevation, with the largest acceleration (100% over 11 days) occurring within 10 km of the margin coincident with spring melt. By late July 2010, 2 weeks before peak melt and runoff, 48 % of the 2400 km2 catchment had slowed to less than the winter mean. This observation supports the hypothesis that the subglacial hydrological system evolves from an inefficient distributed to an efficient drainage system, regulating flow dynamics. Despite this, the cumulative surface flux over the record melt year of 2010 was still greater compared with the perturbation over the average melt year of 2009. This study supports the proposition that local surface meltwater runoff couples to basal hydrology driving ice-sheet dynamics, and although the effect is nonlinear, our observations indicate that greater meltwater runoff yields increased net flux over this sector of the ice sheet.</jats:p

Ascaroside Expression in Caenorhabditis elegans Is Strongly Dependent on Diet and Developmental Stage

Background: The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as “dauer pheromones” because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development. Methodology/Principal Findings: Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions. Conclusions/Significance: Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies

諷刺と警告の書 : アーサー・ミラー『復活ブルース』

Resurrection Blues is Arthur Miller's penultimate play. It is an extreme satirical farce about modern politics, faith and contemporary media-obsessed society. The story is set in an unnamed Latin American country that is a so-called banana republic. A Christ-like man was arrested. He is said to be able to perform miracles and has achieved popularity among the impoverished citizens. The military dictator of the country, Felix, has sentenced him to be crucified and comes up with an idea of selling the rights to broadcast the crucifixion to an American television production team, which would offer big money to him and his country to help the national economy. There are many conflicts among people who urge the crucifixion or try to prevent it. At the end of the play, the Christ-like man disappears without giving any message. Critics have criticized this playas feeble, week. lumbering, rambling or unfinished. Certainly we needn't compare this play with Death of the Salesman or The Crucible. But is this "the great man's Swan song"? Even if it is, this swan is angry against the commercialism of opportunistic media, the venality of politicians, a media-obsessed society, blood-thirsty common people, obsessive religion, and art which takes people's eyes away from the actual reality. This is an imaginary story of an imaginary country, but by writing this play Miller is directing his attention to actual societies, especially the U.S.A. In fact, his characters say, for example, "after they kicked Nixon out of the White House he had one of the biggest funerals since Abraham Lincoln. … nobody clearly remembers anything" or "it's now a quite certain the attack [by a Vietnamese gunboat in the Gulf of Tonkin] never happened. This was a fiction, a poem," or "people are shot on television every ten minutes; bang-bang, and they go down like dolls, it's meaningless." Resurrection Blues makes us recognize our actual worlds - for example, the American media that accompanied by bids to carry the execution of the Oklahoma bomber, Timothy James McVeigh live on the internet, or countries rushing to war under false pretenses after 9/11, or common people concerned about money more than a life or moral. It seems obvious that Miller was conscious of The Crucible when writing Resurrection Blues. Both plays center on religious folks and crushing governors, an injudicious witch-hunt and the planned execution of a seemingly God-like prisoner, as one critic writes. Furthermore, Miller is writing Resurrection Blues in the context of his contemporary worlds, as he was writing The Crucible in the face of McCarthyism. This play gives us a question, "what would happen if Christ were to appear in the world today?" After the Christ-like man disappeared without showing himself and giving any message, a character, who has professed to be his disciple, says, "the actual improvements would just have to be up to us." This satirical farce is Miller's rebuke to the contemporary society and a serious warning to us all. He wants all of us bear responsibility for our future