Cross-protection against European swine influenza viruses in the context of infection immunity against the 2009 pandemic H1N1 virus : studies in the pig model of influenza

Pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. In this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic H1N1 (pH1N1) virus and three different European H1 swine influenza virus (SIV) lineages, and b) these H1 viruses and a European H3N2 SIV. Pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-week intervals between H1 inoculations and between H1 and H3 inoculations, respectively. Virus titers in nasal swabs and/or tissues of the respiratory tract were determined after each inoculation. There was substantial though differing cross-protection between pH1N1 and other H1 viruses, which was directly correlated with the relatedness in the viral hemagglutinin (HA) and neuraminidase (NA) proteins. Cross-protection against H3N2 was almost complete in pigs with immunity against H1N2, but was weak in H1N1/pH1N1-immune pigs. In conclusion, infection with a live, wild type influenza virus may offer substantial cross-lineage protection against viruses of the same HA and/or NA subtype. True heterosubtypic protection, in contrast, appears to be minimal in natural influenza virus hosts. We discuss our findings in the light of the zoonotic and pandemic risks of SIVs

Relevant prior knowledge moderates the effect of elaboration during small group discussion on academic achievement

This study set out to test whether relevant prior knowledge would moderate a positive effect on academic achievement of elaboration during small-group discussion. In a 2 × 2 experimental design, 66 undergraduate students observed a video showing a small-group problem-based discussion about thunder and lightning. In the video, a teacher asked questions to the observing participants. Participants either elaborated by responding to these questions, or did not elaborate, but completed a

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

Effectiveness of neonatal pulse oximetry screening for detection of critical congenital heart disease in daily clinical routine—results from a prospective multicenter study

Pulse oximetry screening (POS) has been proposed as an effective, noninvasive, inexpensive tool allowing earlier diagnosis of critical congenital heart disease (cCHD). Our aim was to test the hypothesis that POS can reduce the diagnostic gap in cCHD in daily clinical routine in the setting of tertiary, secondary and primary care centres. We conducted a prospective multicenter trial in Saxony, Germany. POS was performed in healthy term and post-term newborns at the age of 24–72 h. If an oxygen saturation (SpO2) of ≤95% was measured on lower extremities and confirmed after 1 h, complete clinical examination and echocardiography were performed. POS was defined as false-negative when a diagnosis of cCHD was made after POS in the participating hospitals/at our centre. From July 2006–June 2008, 42,240 newborns from 34 institutions have been included. Seventy-two children were excluded due to prenatal diagnosis (n = 54) or clinical signs of cCHD (n = 18) before POS. Seven hundred ninety-five newborns did not receive POS, mainly due to early discharge after birth (n = 727; 91%). In 41,445 newborns, POS was performed. POS was true positive in 14, false positive in 40, true negative in 41,384 and false negative in four children (three had been excluded for violation of study protocol). Sensitivity, specificity, positive and negative predictive value were 77.78%, 99.90%, 25.93% and 99.99%, respectively. With POS as an adjunct to prenatal diagnosis, physical examination and clinical observation, the percentage of newborns with late diagnosis of cCHD was 4.4%. POS can substantially reduce the postnatal diagnostic gap in cCHD, and false-positive results leading to unnecessary examinations of healthy newborns are rare. POS should be implemented in routine postnatal care

Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.

Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, using pharmacological or genetic approaches, reduces the level of cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signalling and the activation of one of its main downstream targets, fgf20 (ref. 7), which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration

Thalassemias in South Asia:clinical lessons learnt from Bangladesh

Abstract Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world’s thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009–2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries

Induction of Cellular Senescence by Doxorubicin Is Associated with Upregulated miR-375 and Induction of Autophagy in K562 Cells

BACKGROUND: Cellular senescence is a specialized form of growth arrest that is generally irreversible. Upregulated p16, p53, and p21 expression and silencing of E2F target genes have been characterized to promote the establishment of senescence. It can be further aided by the transcriptional repression of proliferation-associated genes by the action of HP1γ, HMGA, and DNMT proteins to produce a repressive chromatin environment. Therefore, senescence has been suggested to functions as a natural brake for tumor development and plays a critical role in tumor suppression and aging. METHODOLOGY/PRINCIPAL FINDINGS: An in vitro senescence model has been established by using K562 cells treated with 50 nM doxorubicin (DOX). Since p53 and p16 are homozygously deleted in the K562 cells, the DOX-induced senescence in K562 cells ought to be independent of p53 and p16-pRb pathways. Indeed, no change in the expression of the typical senescence-associated premalignant cell markers in the DOX-induced senescent K562 cells was found. MicroRNA profiling revealed upregulated miR-375 in DOX-induced senescent K562 cells. Treatment with miR-375 inhibitor was able to reverse the proliferation ability suppressed by DOX (p<0.05) and overexpression of miR-375 suppressed the normal proliferation of K562 cells. Upregulated miR-375 expression was associated with downregulated expression of 14-3-3zeta and SP1 genes. Autophagy was also investigated since DOX treatment was able to induce cells entering senescence and eventually lead to cell death. Among the 24 human autophagy-related genes examined, a 12-fold increase of ATG9B at day 4 and a 20-fold increase of ATG18 at day 2 after DOX treatment were noted. CONCLUSIONS/SIGNIFICANCE: This study has demonstrated that in the absence of p53 and p16, the induction of senescence by DOX was associated with upregulation of miR-375 and autophagy initiation. The anti-proliferative function of miR-375 is possibly exerted, at least in part, by targeting 14-3-3zeta and SP1 genes

The Achievement of a Decentralized Water Management Through Stakeholder Participation: An Example from the Drôme River Catchment Area in France (1981–2008)

International audienceDifferent water Acts (e.g., the European Water Framework Directive) and stakeholders involved in aquatic affairs have promoted integrated river basin management (IRBM) over recent decades. However, few studies have provided feedback on these policies. The aim of the current article is to fill this gap by exploring how local newspapers reflect the implementation of a broad public participation within a catchment of France known for its innovation with regard to this domain. The media coverage of a water management strategy in the Drôme watershed from 1981 to 2008 was investigated using a content analysis and a geographic information system (GIS). We sought to determine what public participation and decentralized decision-making can be in practice. The results showed that this policy was integrated because of its social perspective, the high number of involved stakeholders, the willingness to handle water issues, and the local scale suitable for participation. We emphasized the prominence of the watershed scale guaranteed by the local water authority. This area was also characterized by compromise, arrangements, and power dynamics on a fine scale. We examined the most politically engaged writings regarding water management, which topics each group emphasized, and how the groups agreed and disagreed on issues based on their values and context. The temporal pattern of participation implementation was progressive but worked by fits and starts