112 research outputs found
Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis
Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials
Drug Repurposing: A Systematic Approach to Evaluate Candidate Oral Neuroprotective Interventions for Secondary Progressive Multiple Sclerosis
Objective: To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis. Design: Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action. Results: We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation. Conclusions: We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders
Radiative and magnetohydrodynamics flow of third grade viscoelastic fluid past an isothermal inverted cone in the presence of heat generation/absorption
A mathematical analysis is presented to investigate the nonlinear, isothermal, steady-state, free convection boundary layer flow of an incompressible third grade viscoelastic fluid past an isothermal inverted cone in the presence of magnetohydrodynamic, thermal radiation and heat generation/absorption. The transformed conservation equations for linear momentum, heat and mass are solved numerically subject to the realistic boundary conditions using the second-order accurate implicit finite-difference Keller Box Method. The numerical code is validated with previous studies. Detailed interpretation of the computations is included. The present simulations are of interest in chemical engineering systems and solvent and low-density polymer materials processing
A synthesis of past, current and future research for protection and management of papyrus (Cyperus papyrus L.) wetlands in Africa
Papyrus wetlands (dominated by the giant
sedge Cyperus papyrus L.) occur throughout eastern,
central and southern Africa and are important for
biodiversity, for water quality and quantity regulation
and for the livelihoods of millions of people. To draw
attention to the importance of papyrus wetlands, a
special session entitled ‘‘The ecology of livelihoods in
papyrus wetlands’’ was organized at the 9th INTECOL
Wetlands Conference in Orlando, Florida in June
2012. Papers from the session, combined with additional
contributions, were collected in a special issue
of Wetlands Ecology and Management. The current
paper reviews ecological and hydrological characteristics
of papyrus wetlands, summarizes their ecosystem
services and sustainable use, provides an
overview of papyrus research to date, and looks at
policy development for papyrus wetlands. Based on
this review, the paper provides a synthesis of research
and policy priorities for papyrus wetlands and introduces
the contributions in the special issue. Main
conclusions are that (1) there is a need for better
estimates of the area covered by papyrus wetlands.
Limited evidence suggests that the loss of papyrus
wetlands is rapid in some areas; (2) there is a need for a
better understanding and modelling of the regulating
services of papyrus wetlands to support trade-off
analysis and improve economic valuation; (3) research
on papyrus wetlands should include assessment of all
ecosystem services (provisioning, regulating, habitat,
cultural) so that trade-offs can be determined as the
basis for sustainable management strategies (‘wise
use’); (4) more research on the governance, institutional
and socio-economic aspects of papyrus wetlands
is needed to assist African governments in
dealing with the challenges of conserving wetlands in
the face of growing food security needs and climate
change. The papers in the special issue address a
number of these issues
Invited Commentary: Broadening the Evidence for Adolescent Sexual and Reproductive Health and Education in the United States
Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
Five insights from the Global Burden of Disease Study 2019
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe
A mild thermomechanical process for the enzymatic conversion of radiata pine into fermentable sugars and lignin
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