P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Drug problems among homeless individuals in Toronto, Canada: prevalence, drugs of choice, and relation to health status

<p>Abstract</p> <p>Background</p> <p>Drug use is believed to be an important factor contributing to the poor health and increased mortality risk that has been widely observed among homeless individuals. The objective of this study was to determine the prevalence and characteristics of drug use among a representative sample of homeless individuals and to examine the association between drug problems and physical and mental health status.</p> <p>Methods</p> <p>Recruitment of 603 single men, 304 single women, and 284 adults with dependent children occurred at homeless shelters and meal programs in Toronto, Canada. Information was collected on demographic characteristics and patterns of drug use. The Addiction Severity Index was used to assess whether participants suffered from drug problems. Associations of drug problems with physical and mental health status (measured by the SF-12 scale) were examined using regression analyses.</p> <p>Results</p> <p>Forty percent of the study sample had drug problems in the last 30 days. These individuals were more likely to be single men and less educated than those without drug problems. They were also more likely to have become homeless at a younger age (mean 24.8 vs. 30.9 years) and for a longer duration (mean 4.8 vs. 2.9 years). Marijuana and cocaine were the most frequently used drugs in the past two years (40% and 27%, respectively). Drug problems within the last 30 days were associated with significantly poorer mental health status (-4.9 points, 95% CI -6.5 to -3.2) but not with poorer physical health status (-0.03 points, 95% CI -1.3 to 1.3)).</p> <p>Conclusions</p> <p>Drug use is common among homeless individuals in Toronto. Current drug problems are associated with poorer mental health status but not with poorer physical health status.</p

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

<p>Abstract</p> <p>Background</p> <p>While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile.</p> <p>Methods</p> <p>RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes.</p> <p>Results</p> <p><it>In silico </it>models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells).</p> <p>Conclusion</p> <p>Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.</p

Antenatal risk factors for postnatal depression: a prospective study of chinese women at maternal and child health centres

Background: Risk factors for postnatal depression (PND) are under-explored in the Chinese populations. There is increasing recognition of the importance of identifying predictive factors during the antenatal period for PND. The present study aimed to identify the risk factors for postnatal depression in a community cohort of Chinese women with special focus on the antenatal risk factors.Methods: Eight hundred and five Chinese women were interviewed during their third trimester of pregnancy and at around 2 months postnatally. Putative risk factors for PND were collected and the diagnosis of PND was confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders. The 2-month postnatal depression status was used as the dependent variable for univariate and multivariate analyses against putative risk factors.Results: Marital dissatisfaction (Relative Risk = 8.27), dissatisfied relationship with mother-in-law (Relative Risk = 3.93), antenatal depressive symptomatology (Relative Risk = 3.90), and anxiety-prone personality (Relative Risk = 2.14) predicted PND in Chinese women independently.Conclusions: Chinese women tend to keep their own feelings and emotions and it is important to monitor Chinese pregnant women with these predictive risk factors so that PND can be identified early. © 2012 Siu et al; licensee BioMed Central Ltd.published_or_final_versio

Whales, dolphins or fishes? The ethnotaxonomy of cetaceans in São Sebastião, Brazil

The local knowledge of human populations about the natural world has been addressed through ethnobiological studies, especially concerning resources uses and their management. Several criteria, such as morphology, ecology, behavior, utility and salience, have been used by local communities to classify plants and animals. Studies regarding fishers' knowledge on cetaceans in the world, especially in Brazil, began in the last decade. Our objective is to investigate the folk classification by fishers concerning cetaceans, and the contribution of fishers' local knowledge to the conservation of that group. In particular, we aim to record fishers' knowledge in relation to cetaceans, with emphasis on folk taxonomy. The studied area is São Sebastião, located in the southeastern coast of Brazil, where 70 fishers from 14 communities were selected according to their fishing experience and interviewed through questionnaires about classification, nomenclature and ecological aspects of local cetaceans' species. Our results indicated that most fishers classified cetaceans as belonging to the life-form 'fish'. Fishers' citations for the nomenclature of the 11 biological species (10 biological genera), resulted in 14 folk species (3 generic names). Fishers' taxonomy was influenced mostly by the phenotypic and cultural salience of the studied cetaceans. Cultural transmission, vertical and horizontal, was intimately linked to fishers' classification process. The most salient species, therefore well recognized and named, were those most often caught by gillnets, in addition to the biggest ones and those most exposed by media, through TV programs, which were watched and mentioned by fishers. Our results showed that fishers' ecological knowledge could be a valuable contribution to cetaceans' conservation, helping to determine areas and periods for their protection, indicating priority topics for research and participating in alternative management related to the gillnet fisheries

'Physical activity at home (PAAH)', evaluation of a group versus home based physical activity program in community dwelling middle aged adults: rationale and study design

<p>Abstract</p> <p>Background</p> <p>It is well recognised that the adoption and longer term adherence to physical activity by adults to reduce the risk of chronic disease is a challenge. Interventions, such as group and home based physical activity programs, have been widely reported upon. However few studies have directly compared these interventions over the longer term to determine their adherence and effectiveness. Participant preference for home based or group interventions is important. Some evidence suggests that home based physical activity programs are preferred by middle aged adults and provide better long term physical activity adherence. Physiotherapists may also be useful in increasing physical activity adherence, with limited research on their impact.</p> <p>Methods</p> <p>'Physical Activity at Home' is a 2 year pragmatic randomised control trial, with a non-randomised comparison to group exercise. Middle-aged adults not interested in, or unable to attend, a group exercise program will be targeted. Sedentary community dwelling 50-65 year olds with no serious medical conditions or functional impairments will be recruited via two mail outs using the Australian federal electoral roll. The first mail out will invite participants to a 6 month community group exercise program. The second mail out will be sent to those not interested in the group exercise program inviting them to take part in a home based intervention. Eligible home based participants will be randomised into a 6 month physiotherapy-led home based physical activity program or usual care. Outcome measures will be taken at baseline, 6, 12, 18 and 24 months. The primary outcome is physical activity adherence via exercise diaries. Secondary outcomes include the Active Australia Survey, accelerometry, aerobic capacity (step test), quality of life (SF-12v2), blood pressure, waist circumference, waist-to-hip ratio and body mass index. Costs will be recorded prospectively and qualitative data will be collected.</p> <p>Discussion</p> <p>The planned 18 month follow-up post intervention will provide an indication of the effectiveness of the group and home based interventions in terms of adherence to physical activity, health benefits and cost. If the physiotherapy-led home based physical activity program is successful it could provide an alternative option for physical activity program delivery across a number of settings.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12611000890932.aspx">ACTRN12611000890932</a></p

First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

Congenital toxoplasmosis can result in permanent sequel as blindness or neurological damage in children and it seems to be more severe in South America than in other continents. There is a lack of information about this frequency in Colombia, where no control program is established, although it is a recognized cause of potentially preventable congenital blindness. We propose the first Colombian multicentric study to determine the frequency and impact of congenital toxoplasmosis. More than 15,000 newborns in seven cities were studied. Newborns were tested at birth by doing a cord blood test for toxoplasmosis. Additionally, children from mothers with history of toxoplasmosis acquired during pregnancy were recalled for a follow-up. The program identified fifteen children otherwise undiagnosed; three of these children died as consequence of congenital toxoplasmosis. The frequency of the congenital infection varied significantly between cities, being higher in Armenia and Florencia, intermediate in Bogota, Bucaramanga and Barranquilla and very low in western cities such as Cucuta and Riohacha. For the first time a significant correlation was found between mean rainfall at the city and the incidence of this congenital infection

Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes

Malaria (Plasmodium spp.) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies. The most important human malaria parasite, Plasmodium falciparum, undergoes a complex developmental cycle in the mosquito that takes approximately two weeks and begins with the invasion of the mosquito midgut. Here, we demonstrate that increased Akt signaling in the mosquito midgut disrupts parasite development and concurrently reduces the duration that mosquitoes are infective to humans. Specifically, we found that increased Akt signaling in the midgut of heterozygous Anopheles stephensi reduced the number of infected mosquitoes by 60–99%. Of those mosquitoes that were infected, we observed a 75–99% reduction in parasite load. In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked. The increase in midgut-specific Akt signaling also led to an 18–20% reduction in the average mosquito lifespan. Thus, activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity