137 research outputs found
Development of a Core Outcome Set and Minimum Reporting Set for intervention studies in growth restriction in the NEwbOrN (COSNEON): study protocol for a Delphi study.
BACKGROUND: Growth restriction in the newborn (GRN) can predispose to severe complications including hypoglycemia, sepsis, and necrotizing enterocolitis. Different interventions and treatments, such as feeding strategies, for GRN have specific benefits and risks. Comparing results from studies investigating intervention studies in GRN is challenging due to the use of different baseline and study characteristics and differences in reported study outcomes. In order to be able to compare study results and to allow pooling of data, uniform reporting of study characteristics (minimum reporting set [MRS]) and outcomes (core outcome set [COS]) are needed. We aim to develop both an MRS and a COS for interventional and treatment studies in GRN. METHODS/DESIGN: The MRS and COS will be developed according to Delphi methodology. First, a scoping literature search will be performed to identify study characteristics and outcomes in research focused on interventions/treatments in the GRN. An international group of stakeholders, including experts (clinicians working with GRN, and researchers who focus on GRN) and lay experts ([future] parents of babies with GRN), will be questioned to rate the importance of the study characteristics and outcomes in three rounds. After three rounds there will be two consensus meetings: a face-to-face meeting and an electronic meeting. During the consensus meetings multiple representatives of stakeholder groups will reach agreement upon which study characteristics and outcomes will be included into the COS and MRS. The second electronic consensus meeting will be used to test if an electronic meeting is as effective as a face-to-face meeting. DISCUSSION: In our opinion a COS alone is not sufficient to compare and aggregate trial data. Hence, to ensure optimum comparison we also will develop an MRS. Interventions in GRN infants are often complicated by coexisting preterm birth. A COS already has been developed for preterm birth. The majority of GRN infants are born at term, however, and we therefore chose to develop a separate COS for interventions in GRN, which can be combined (with expected overlap) in intervention studies enrolling preterm GRN babies. TRIAL REGISTRATION: Not applicable. This study is registered in the Core Outcome Measures for Effectiveness ( COMET ) database. Registered on 30 June 2017
A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita
© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio
Self-Protective Function of Post-Conflict Bystander Affiliation in Mandrills
Background: Affiliative interactions exchanged between victims of aggression and individuals not involved in the original aggression (bystanders) have been observed in various species. Three hypothetical functions have been proposed for these interactions: consolation, self-protection and substitute reconciliation, but data to test them are scanty. Methodology/Principal Findings: We conducted post-conflict and matched control observations on a captive group of mandrills (Mandrillus sphinx). We found that victims often redirected aggression to bystanders, that they received most affiliation from those bystanders that were frequently the target of redirection, and that bystander affiliation reduced the likelihood of redirection. Bystander affiliation did not reduce the victim\u27s distress (as measured by its scratching rates) and was not received primarily from kin/friends. Finally, bystander affiliation did not reduce the likelihood of renewed aggression from the original aggressor. Conclusions/Significance: These results provide support for the self-protection hypothesis but not for the consolation and substitute reconciliation hypotheses
Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis
<p>Abstract</p> <p>Background</p> <p>The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.</p> <p>Methods</p> <p>Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.</p> <p>Results</p> <p>Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and D<sub>LCO </sub>were independent predictors of systolic pulmonary artery pressure.</p> <p>Conclusion</p> <p>Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.</p
Assessing vulnerability: an integrated approach for mapping adaptive capacity, sensitivity, and exposure
Bordetella pertussis Autotransporter Vag8 Binds Human C1 Esterase Inhibitor and Confers Serum Resistance
Bordetella pertussis employs numerous strategies to evade the immune system, including the ability to resist killing via complement. Previously we have shown that B. pertussis binds a complement regulatory protein, C1 esterase inhibitor (C1inh) to its surface in a Bvg-regulated manner (i.e. during its virulence phase), but the B. pertussis factor was not identified. Here we set out to identify the B. pertussis C1inh-binding factor. Using a serum overlay assay, we found that this factor migrates at approximately 100 kDa on an SDS-PAGE gel. To identify this factor, we isolated proteins of approximately 100 kDa from wild type strain BP338 and from BP347, an isogenic Bvg mutant that does not bind C1inh. Using mass spectrometry and bioinformatics, we identified the autotransporter protein Vag8 as the putative C1inh binding protein. To prove that Vag8 binds C1inh, vag8 was disrupted in two different B. pertussis strains, namely BP338 and 18–323, and the mutants were tested for their ability to bind C1inh in a surface-binding assay. Neither mutant strain was capable of binding C1inh, whereas a complemented strain successfully bound C1inh. In addition, the passenger domain of Vag8 was expressed and purified as a histidine-tagged fusion protein and tested for C1inh-binding in an ELISA assay. Whereas the purified Vag8 passenger bound C1inh, the passenger domain of BrkA (a related autotransporter protein) failed to do so. Finally, serum assays were conducted to compare wild type and vag8 mutants. We determined that vag8 mutants from both strains were more susceptible to killing compared to their isogenic wild type counterparts. In conclusion, we have discovered a novel role for the previously uncharacterized protein Vag8 in the immune evasion of B. pertussis. Vag8 binds C1inh to the surface of the bacterium and confers serum resistance
Identifying and tracking key climate adaptation actors in the UK
To understand how climate adaptation planning and decision-making will progress, a better understanding is needed as to which organisations are expected to take on key responsibilities. Methodological challenges have impeded efforts to identify and track adaptation actors beyond the coarse scale of nation states. Yet, for effective adaptation to succeed, who do national governments need to engage, support and encourage? Using the UK as a case study, we conducted a systematic review of official government documents on climate adaptation, between 2006 and 2015, to understand which organisations are identified as key to future adaptation efforts and tracked the extent to which these organisations changed over time. Our unique longitudinal dataset found a very large number of organisations (n = 568). These organisations varied in size (small-medium enterprises to large multinationals), type (public, private and not-for-profit), sector (e.g. water, energy, transport and health), scale (local, national and international), and roles and responsibilities (policymaking, decision-making, knowledge production, retail). Importantly, our findings reveal a mismatch between official government policies that repeatedly call on private organisations to drive adaptation, on the one hand, and a clear dominance of the public sector on the other hand. Yet, the capacity of organisations to fulfil the roles and responsibilities assigned to them, particularly in the public sector, is diminishing. Unless addressed, climate adaptation actions could be assigned to those either unable, or unwilling, to implement them
Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH
Cyanobacterial lipopolysaccharides and human health – a review
Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation
Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary
There has been considerable investigation of the potential for soyfoods to reduce risk of cancer, and in particular cancer of the breast. Most interest in this relationship is because soyfoods are essentially a unique dietary source of isoflavones, compounds which bind to estrogen receptors and exhibit weak estrogen-like effects under certain experimental conditions. In recent years the relationship between soyfoods and breast cancer has become controversial because of concerns – based mostly on in vitro and rodent data – that isoflavones may stimulate the growth of existing estrogen-sensitive breast tumors. This controversy carries considerable public health significance because of the increasing popularity of soyfoods and the commercial availability of isoflavone supplements. In this analysis and commentary we attempt to outline current concerns regarding the estrogen-like effects of isoflavones in the breast focusing primarily on the clinical trial data and place these concerns in the context of recent evidence regarding estrogen therapy use in postmenopausal women. Overall, there is little clinical evidence to suggest that isoflavones will increase breast cancer risk in healthy women or worsen the prognosis of breast cancer patients. Although relatively limited research has been conducted, and the clinical trials often involved small numbers of subjects, there is no evidence that isoflavone intake increases breast tissue density in pre- or postmenopausal women or increases breast cell proliferation in postmenopausal women with or without a history of breast cancer. The epidemiologic data are generally consistent with the clinical data, showing no indication of increased risk. Furthermore, these clinical and epidemiologic data are consistent with what appears to be a low overall breast cancer risk associated with pharmacologic unopposed estrogen exposure in postmenopausal women. While more research is required to definitively allay concerns, the existing data should provide some degree of assurance that isoflavone exposure at levels consistent with historical Asian soyfood intake does not result in adverse stimulatory effects on breast tissue
- …