Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats

<p>Abstract</p> <p>Background</p> <p>Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of such cross-protection showed that cytotoxic T lymphocytes (CTL) protect H3N2-immune mice from a lethal H1N1 infection. More recent studies in mice demonstrate that antibodies also contribute to heterosubtypic immunity (HSI). We previously demonstrated that HSI in cotton rats (<it>Sigmodon hispidus</it>) is characterized by protection of H3N2-immune animals from influenza H1N1-induced increase in respiratory rate (tachypnea). Alternatively, H1N1-immune animals are protected from H3N2-induced tachypnea. The experiments described in this report were designed to elucidate the immune mechanism that prevents this very early sign of disease.</p> <p>Results</p> <p>Our results show that cotton rats provided with H1N1-immune serum prior to challenge with an H3N2 virus were protected from influenza-associated tachypnea, with the degree of protection correlating with the antibody titer transferred. Immunization with an inactivated preparation of virus delivered intramuscularly also provided some protection suggesting that CTL and/or mucosal antibody responses are not required for protection. Antibodies specific for conserved epitopes present on the virus exterior are likely to facilitate this protection since prophylactic treatment of cotton rats with anti-M2e (the extracellular domain of M2) but not anti-nucleoprotein (NP) reduced virus-induced tachypnea.</p> <p>Conclusion</p> <p>In the cotton rat model of heterosubtypic immunity, humoral immunity plays a role in protecting animals from influenza-induced tachypea. Partial protection against respiratory disease caused by different influenza A subtypes can be attained with either live virus administered intranasally or inactivated virus delivered intramuscularly suggesting that either vaccine regimen may provide some protection against potential pandemic outbreaks in humans.</p

CACHD1 is an α2δ-like protein that modulates CaV3 voltage-gated calcium channel activity

The putative cache (Ca2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the alpha2delta voltage-gated Ca2+ channel (VGCC) auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus and cerebellum, with a broadly similar tissue distribution to CaV3 subunits, in particular, CaV3.1. In expression studies, CACHD1 increased cell-surface localization of CaV3.1 and these proteins were in close proximity at the cell surface consistent with the formation of CACHD1-CaV3.1 complexes. In functional electrophysiological studies, co-expression of human CACHD1 with CaV3.1, CaV3.2 and CaV3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, alpha2delta-1 had no effect on peak current density or maximal conductance in either CaV3.1, CaV3.2 or CaV3.3. Comparison of CACHD1-mediated increases in CaV3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female E19 rats, CACHD1 overexpression increased CaV3-mediated action potential (AP) firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an alpha2delta-like protein that functionally modulates CaV3 voltage-gated calcium channel activity

Randomized controlled trials in pediatric complementary and alternative medicine: Where can they be found?

BACKGROUND: The safety and effectiveness of CAM interventions are of great relevance to pediatric health care providers. The objective of this study is to identify sources of reported randomized controlled trials (RCTs) in the field of pediatric complementary and alternative medicine (CAM). METHODS: Reports of RCTs were identified by searching Medline and 12 additional bibliographic databases and by reviewing the reference lists of previously identified pediatric CAM systematic reviews. RESULTS: We identified 908 reports of RCTs that included children under 18 and investigated a CAM therapy. Since 1965, there has been a steady growth in the number of these trials that are being published. The four journals that published the most reported RCTs are The American Journal of Clinical Nutrition, Pediatrics, Journal of Pediatrics, and Lancet. Medline, CAB Health, and Embase were the best database sources for identifying these studies; they indexed 93.2%, 58.4% and 42.2 % respectively of the journals publishing reports of pediatric CAM RCTs. CONCLUSIONS: Those working or interested in the field of pediatric CAM should routinely search Medline, CAB Health and Embase for literature in the field. The four core journals identified above should be included in their collection

Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

<p>Abstract</p> <p>Background</p> <p>Increased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (<it>Sigmodon hispidus</it>) also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection.</p> <p>Methods</p> <p>Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old) and adult (6–12 week old) cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph.</p> <p>Results</p> <p>Adult cotton rats had significantly greater tidal volume (TV), and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (<it>Penh</it>) during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult) cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to <it>Penh </it>were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in <it>Penh </it>in infant animals.</p> <p>Conclusion</p> <p>While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume) is increased in the infant animals only. This is likely to be a consequence of greater lung elastance in the very young animals. This model replicates many respiratory features of humans and consequently may be a useful tool to investigate new strategies to treat respiratory disease in influenza-infected infants.</p

Transmission of Avian Influenza A Viruses among Species in an Artificial Barnyard

Waterfowl and shorebirds harbor and shed all hemagglutinin and neuraminidase subtypes of influenza A viruses and interact in nature with a broad range of other avian and mammalian species to which they might transmit such viruses. Estimating the efficiency and importance of such cross-species transmission using epidemiological approaches is difficult. We therefore addressed this question by studying transmission of low pathogenic H5 and H7 viruses from infected ducks to other common animals in a quasi-natural laboratory environment designed to mimic a common barnyard. Mallards (Anas platyrhynchos) recently infected with H5N2 or H7N3 viruses were introduced into a room housing other mallards plus chickens, blackbirds, rats and pigeons, and transmission was assessed by monitoring virus shedding (ducks) or seroconversion (other species) over the following 4 weeks. Additional animals of each species were directly inoculated with virus to characterize the effect of a known exposure. In both barnyard experiments, virus accumulated to high titers in the shared water pool. The H5N2 virus was transmitted from infected ducks to other ducks and chickens in the room either directly or through environmental contamination, but not to rats or blackbirds. Ducks infected with the H7N2 virus transmitted directly or indirectly to all other species present. Chickens and blackbirds directly inoculated with these viruses shed significant amounts of virus and seroconverted; rats and pigeons developed antiviral antibodies, but, except for one pigeon, failed to shed virus

The association between socioeconomic status and traditional chinese medicine use among children in Taiwan

<p>Abstract</p> <p>Background</p> <p>Traditional Chinese medicine (TCM) utilization is common in Asian countries. Limited studies are available on the socioeconomic status (SES) associated with TCM use among the pediatric population. We report on the association between SES and TCM use among children and adolescents in Taiwan.</p> <p>Methods</p> <p>A National Health Interview Survey was conducted in Taiwan in 2001 that included 5,971 children and adolescents. We assessed the children's SES using the head of household's education, occupation and income. This information was used to calculate pediatric SES scores, which in turn were divided into quartiles. Children and adolescents who visited TCM in the past month were defined as TCM users.</p> <p>Results</p> <p>Compared to children in the second SES quartile, children in the fourth SES quartile had a higher average number of TCM visits (0.12 vs. 0.06 visits, p = 0.027) and higher TCM use prevalence (5.0% vs. 3.6%, p = 0.024) within the past month. The adjusted odds ratio (OR) for TCM use was higher for children in the fourth SES quartile than for those in the first SES quartile (OR 1.49; 95% confidence interval [CI] 1.02-2.17). The corresponding OR was 2.17 for girls (95% CI 1.24-3.78). The highest-SES girls (aged 10-18 years) were most likely to visit TCM practices (OR 2.47; 95% CI 1.25-4.90).</p> <p>Conclusions</p> <p>Children and adolescents with high SES were more likely to use TCM and especially girls aged 10-18 years. Our findings point to the high use of complementary and alternative medicine among children and adolescents.</p

How parents choose to use CAM: a systematic review of theoretical models

Background: Complementary and Alternative Medicine (CAM) is widely used throughout the UK and the Western world. CAM is commonly used for children and the decision-making process to use CAM is affected by numerous factors. Most research on CAM use lacks a theoretical framework and is largely based on bivariate statistics. The aim of this review was to identify a conceptual model which could be used to explain the decision-making process in parental choice of CAM. Methods: A systematic search of the literature was carried out. A two-stage selection process with predetermined inclusion/exclusion criteria identified studies using a theoretical framework depicting the interaction of psychological factors involved in the CAM decision process. Papers were critically appraised and findings summarised. Results: Twenty two studies using a theoretical model to predict CAM use were included in the final review; only one examined child use. Seven different models were identified. The most commonly used and successful model was Andersen's Sociobehavioural Model (SBM). Two papers proposed modifications to the SBM for CAM use. Six qualitative studies developed their own model. Conclusion: The SBM modified for CAM use, which incorporates both psychological and pragmatic determinants, was identified as the best conceptual model of CAM use. This model provides a valuable framework for future research, and could be used to explain child CAM use. An understanding of the decision making process is crucial in promoting shared decision making between healthcare practitioners and parents and could inform service delivery, guidance and policy

The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe