The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.Portuguese Foundation for Science and Technology (FCT), the strategic funding of UID/BIO/04469/2013-CEB and UID/EQU/00511/2013-LEPABE units. This study was also supported by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects “DNA mimics” PIC/IC/82815/2007, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), “BioHealth—Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027 and NORTE-07-0124-FEDER-000025—RL2_ Environment and Health, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the grant of Susana P. Lopes (SFRH/BPD/95616/2013) and of the COST-Action TD1004: Theragnostics for imaging and therapy

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

The Nexus Solutions Tool (NEST): An open platform for optimizing multi-scale energy-water-land system transformations

The energy-water-land nexus represents a critical leverage future policies must draw upon to reduce trade-offs between sustainable development objectives. Yet, existing long-term planning tools do not provide the scope or level of integration across the nexus to unravel important development constraints. Moreover, existing tools and data are not always made openly available or are implemented across disparate modeling platforms that can be difficult to link directly with modern scientific computing tools and databases. In this paper, we present the Nexus Solutions Tool (NEST): a new open modeling platform that integrates multi-scale energy-water-land resource optimization with distributed hydrological modeling. The new approach provides insights into the vulnerability of water, energy and land resources to future socioeconomic and climatic change and how multi-sectoral policies, technological solutions and investments can improve the resilience and sustainability of transformation pathways while avoiding counterproductive interactions among sectors. NEST can be applied at different spatial and temporal resolutions, and is designed specifically to tap into the growing body of open access geospatial data available through national inventories and the earth system modeling community. A case study analysis of the Indus River Basin in South Asia demonstrates the capability of the model to capture important interlinkages across system transformation pathways towards the United Nations' Sustainable Development Goals, including the intersections between local and regional transboundary policies and incremental investment costs from rapidly increasing regional consumption projected over the coming decades

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

The results of arthroscopic anterior stabilisation of the shoulder using the bioknotless anchor system

<p>Abstract</p> <p>Background</p> <p>Shoulder instability is a common condition, particularly affecting a young, active population. Open capsulolabral repair is effective in the majority of cases, however arthroscopic techniques, particularly using suture anchors, are being used with increasing success.</p> <p>Methods</p> <p>15 patients with shoulder instability were operated on by a single surgeon (VK) using BioKnotless anchors (DePuy Mitek, Raynham, MA). The average length of follow-up was 21 months (17 to 31) with none lost to follow-up. Constant scores in both arms, patient satisfaction, activity levels and recurrence of instability was recorded.</p> <p>Results</p> <p>80% of patients were satisfied with their surgery. 1 patient suffered a further dislocation and another had recurrent symptomatic instability. The average constant score returned to 84% of that measured in the opposite (unaffected) shoulder. There were no specific post-operative complications encountered.</p> <p>Conclusion</p> <p>In terms of recurrence of symptoms, our results show success rates comparable to other methods of shoulder stabilisation. This technique is safe and surgeons familiar with shoulder arthroscopy will not encounter a steep learning curve. Shoulder function at approximately 2 years post repair was good or excellent in the majority of patients and it was observed that patient satisfaction was correlated more with return to usual activities than recurrence of symptoms.</p

A single dose of pegfilgrastim compared with daily filgrastim for supporting neutrophil recovery in patients treated for low-to-intermediate risk acute myeloid leukemia: results from a randomized, double-blind, phase 2 trial

Background: Patients with acute myeloid leukemia (AML) are often neutropenic as a result of their disease. Furthermore, these patients typically experience profound neutropenia following induction and/or consolidation chemotherapy and this may result in serious, potentially life-threatening, infection. This randomized, double-blind, phase 2 clinical trial compared the efficacy and tolerability of pegfilgrastim with filgrastim for assisting neutrophil recovery following induction and consolidation chemotherapy for de novo AML in patients with low-to-intermediate risk cytogenetics. Methods: Patients (n = 84) received one or two courses of standard induction chemotherapy (idarubicin + cytarabine), followed by one course of consolidation therapy (high-dose cytarabine) if complete remission was achieved. They were randomized to receive either single-dose pegfilgrastim 6 mg or daily filgrastim 5 μg/kg, beginning 24 hours after induction and consolidation chemotherapy. Results: The median time to recovery from severe neutropenia was 22.0 days for both pegfilgrastim (n = 42) and filgrastim (n = 41) groups during Induction 1 (difference 0.0 days; 95% CI: -1.9 to 1.9). During Consolidation, recovery occurred after a median of 17.0 days for pegfilgrastim versus 16.5 days for filgrastim (difference 0.5 days; 95% CI: -1.1 to 2.1). Therapeutic pegfilgrastim serum concentrations were maintained throughout neutropenia. Pegfilgrastim was well tolerated, with an adverse event profile similar to that of filgrastim. Conclusion: These data suggest no clinically meaningful difference between a single dose of pegfilgrastim and multiple daily doses of filgrastim for shortening the duration of severe neutropenia following chemotherapy in de novo AML patients with low-to-intermediate risk cytogenetics

Sexual Conflict and Sexually Antagonistic Coevolution in an Annual Plant

BACKGROUND: Sexual conflict theory predicts sexually antagonistic coevolution of reproductive traits driven by conflicting evolutionary interests of two reproducing individuals. Most studies of the evolutionary consequences of sexual conflicts have, however, to date collectively investigated only a few species. In this study we used the annual herb Collinsia heterophylla to experimentally test the existence and evolutionary consequences of a potential sexual conflict over onset of stigma receptivity. METHODOLOGY/PRINCIPAL FINDINGS: We conducted crosses within and between four greenhouse-grown populations originating from two regions. Our experimental setup allowed us to investigate male-female interactions at three levels of geographic distances between interacting individuals. Both recipient and pollen donor identity affected onset of stigma receptivity within populations, confirming previous results that some pollen donors can induce stigma receptivity. We also found that donors were generally better at inducing stigma receptivity following pollen deposition on stigmas of recipients from another population than their own, especially within a region. On the other hand, we found that donors did worse at inducing stigma receptivity in crosses between regions. Interestingly, recipient costs in terms of lowered seed number after early fertilisation followed the same pattern: the cost was apparent only if the pollen donor belonged to the same region as the recipient. CONCLUSION/SIGNIFICANCE: Our results indicate that recipients are released from the cost of interacting with local pollen donors when crossed with donors from a more distant location, a pattern consistent with a history of sexually antagonistic coevolution within populations. Accordingly, sexual conflicts may have important evolutionary consequences also in plants

Healthcare-associated viral and bacterial infections in dentistry

Infection prevention in dentistry is an important topic that has gained more interest in recent years and guidelines for the prevention of cross-transmission are common practice in many countries. However, little is known about the real risks of cross-transmission, specifically in the dental healthcare setting. This paper evaluated the literature to determine the risk of cross-transmission and infection of viruses and bacteria that are of particular relevance in the dental practice environment. Facts from the literature on HSV, VZV, HIV, Hepatitis B, C and D viruses, Mycobacterium spp., Pseudomonas spp., Legionella spp. and multi-resistant bacteria are presented. There is evidence that Hepatitis B virus is a real threat for cross-infection in dentistry. Data for the transmission of, and infection with, other viruses or bacteria in dental practice are scarce. However, a number of cases are probably not acknowledged by patients, healthcare workers and authorities. Furthermore, cross-transmission in dentistry is under-reported in the literature. For the above reasons, the real risks of cross-transmission are likely to be higher. There is therefore a need for prospective longitudinal research in this area, to determine the real risks of cross-infection in dentistry. This will assist the adoption of effective hygiene procedures in dental practice

Regulation of Retinoid Receptors by Retinoic Acid and Axonal Contact in Schwann Cells

Background: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type. Methodology/Principal Findings: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-c depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-c mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-b mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without changes in mRNA stability. Conclusions/Significance: All together, our results show that retinoid receptors are regulated in a complex manner i