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Cholesterol lowering treatment restores blood global DNA methylation in chronic kidney disease (CKD) patients
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This author accepted manuscript is made available following 12 month embargo from date of publication (June 2017) in accordance with the publisher’s archiving policyBackground and aims
Chronic kidney disease (CKD) is characterized by increased oxidative stress (OS). In consideration of the well-known link between OS and DNA methylation we assessed DNA methylcytosine (mCyt) concentrations in CKD patients at baseline and during cholesterol lowering treatment.
Methods and results
DNA methylation and OS indices (malonyldialdehyde, MDA; allantoin/uric acid ratio, All/UA) were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20 mg/day, or ezetimibe/simvastatin 10/40 mg/day) and 30 age- and sex-matched healthy controls. DNA methylation was significantly lower in CKD patients vs. controls (4.06 ± 0.20% vs. 4.27 ± 0.17% mCyt, p = 0.0001). Treatment significantly increased mCyt DNA concentrations in all patients (4.06 ± 0.04% at baseline; 4.12 ± 0.03% at 4 months; 4.17 ± 0.03% at 8 months; and 4.20 ± 0.02% at 12 months, p = 0.0001 for trend). A trend for a greater effect on DNA methylation was observed with combined treatment ezetimibe/simvastatin 10/40 mg/day (+5.2% after one year treatment). The treatment-associated mCyt increase was significantly correlated with the concomitant reduction in MDA concentrations and All/AU ratios.
Conclusion
Our results demonstrate that CKD patients have a lower degree of DNA methylation and that cholesterol lowering treatment restores mCyt DNA concentrations to levels similar to healthy controls. The treatment-associated increase in DNA methylation is correlated with a concomitant reduction in OS markers.
The study was registered at clinicaltrials.gov (NCT00861731)
Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.There is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4+ T cells (IFN-γ+TNF+IL-2+). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (AdvaxCpG), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/AdvaxCpG resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4+ T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/AdvaxCpG is a strong candidate for further preclinical evaluation for progression to human trials
Characteristics and causal factors of hysteresis in the hydrodynamics of a large floodplain system: Poyang Lake (China)
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (Aug 2017) in accordance with the publisher’s archiving policyA previous modeling study of the lake-floodplain system of Poyang Lake (China) revealed complex hysteretic relationships between stage, storage volume and surface area. However, only hypothetical causal factors were presented, and the reasons for the occurrence of both clockwise and counterclockwise hysteretic functions were unclear. The current study aims to address this by exploring further Poyang Lake’s hysteretic behavior, including consideration of stage-flow relationships. Remotely sensed imagery is used to validate the water surface areas produced by hydrodynamic modeling. Stage-area relationships obtained using the two methods are in strong agreement. The new results reveal a three-phase hydrological regime in stage-flow relationships, which assists in developing improved physical interpretation of hysteretic stage-area relationships for the lake-floodplain system. For stage-area relationships, clockwise hysteresis is the result of classic floodplain hysteretic processes (e.g., restricted drainage of the floodplain during recession), whereas counterclockwise hysteresis derives from the river hysteresis effect (i.e., caused by backwater effects). The river hysteresis effect is enhanced by the time lag between the peaks of catchment inflow and Yangtze discharge (i.e., the so-called Yangtze River blocking effect). The time lag also leads to clockwise hysteresis in the relationship between Yangtze River discharge and lake stage. Thus, factors leading to hysteresis in other rivers, lakes and floodplains act in combination within Poyang Lake to create spatial variability in hydrological hysteresis. These effects dominate at different times, in different parts of the lake, and during different phases of the lake’s water level fluctuations, creating the unique hysteretic hydrological behavior of Poyang Lake
A fully continuous system of DNA profile evidence evaluation that can utilise STR profile data produced under different conditions within a single analysis
Get PDF© 2017 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/The introduction of probabilistic DNA interpretation systems has made it possible to evaluate many profiles that previously (under a manual interpretation system) were not. These probabilistic systems have been around for a number of years and it is becoming more common that their use within a laboratory has spanned at least one technology change. This may be a change in laboratory hardware, the DNA profiling kit used, or the manner in which the profile is generated. Up until this point, when replicates DNA profiles are generated, that span a technological change, the ability to utilise all the information in all replicates has been limited or non-existent. In this work we explain and derive the models required to evaluate (what we term) multi-kit analysis problems. We demonstrate the use of the multi-kit feature on a number of scenarios where such an analysis would be desired within a laboratory. Allowing the combination of profiling data that spans a technological change will further increase the amount of DNA profile information produced in a laboratory that can be evaluated
Characteristics of Smartphone Applications for Nutrition Improvement in Community Settings: A Scoping Review
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Copyright © 2019 American Society for NutritionSmartphone applications are increasingly being used to support nutrition improvement in community settings. However, there is a scarcity of practical literature to support researchers and practitioners in choosing or developing health applications. This work maps the features, key content, theoretical approaches, and methods of consumer testing of applications intended for nutrition improvement in community settings. A systematic, scoping review methodology was used to map published, peer-reviewed literature reporting on applications with a specific nutrition-improvement focus intended for use in the community setting. After screening, articles were grouped into 4 categories: dietary self-monitoring trials, nutrition improvement trials, application description articles, and qualitative application development studies. For mapping, studies were also grouped into categories based on the target population and aim of the application or program. Of the 4818 titles identified from the database search, 64 articles were included. The broad categories of features found to be included in applications generally corresponded to different behavior change support strategies common to many classic behavioral change models. Key content of applications generally focused on food composition, with tailored feedback most commonly used to deliver educational content. Consumer testing before application deployment was reported in just over half of the studies. Collaboration between practitioners and application developers promotes an appropriate balance of evidence-based content and functionality. This work provides a unique resource for program development teams and practitioners seeking to use an application for nutrition improvement in community settings
Online path planning for AUV rendezvous in dynamic cluttered undersea environment using evolutionary algorithms
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This author accepted manuscript is made available following 24 month embargo from date of publication (October 2017) in accordance with the publisher’s archiving policyIn this study, a single autonomous underwater vehicle (AUV) aims to rendezvous with a submerged leader recovery vehicle through a cluttered and variable operating field. The rendezvous problem is transformed into a Nonlinear Optimal Control Problem (NOCP) and then numerical solutions are provided. A penalty function method is utilized to combine the boundary conditions, vehicular and environmental constraints with the performance index that is final rendezvous time. Four evolutionary based path planning methods namely Particle Swarm Optimization (PSO), Biogeography-Based Optimization (BBO), Differential Evolution (DE), and Firefly Algorithm (FA) are employed to establish a reactive planner module and provide a numerical solution for the proposed NOCP. The objective is to synthesize and analyze the performance and capability of the mentioned methods for guiding an AUV from an initial loitering point toward the rendezvous through a comprehensive simulation study. The proposed planner module entails a heuristic for refining the path considering situational awareness of environment, encompassing static and dynamic obstacles within a spatiotemporal current fields. The planner thus needs to accommodate the unforeseen changes in the operating field such as emergence of unpredicted obstacles or variability of current field and turbulent regions. The simulation results demonstrate the inherent robustness and efficiency of the proposed planner for enhancing a vehicle’s autonomy so as to enable it to reach the desired rendezvous. The advantages and shortcoming of all utilized methods are also presented based on the obtained results
Quality of missing data reporting and handling in palliative care trials demonstrates that further development of the CONSORT statement is required: a systematic review
Get PDFPublished by Elsevier Inc. This is an open access article under the CC BY-NCND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Objectives: Assess (i) the quality of reporting and handling of missing data (MD) in palliative care trials, (ii) whether there are differences in the reporting of criteria specified by the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement compared with those not specified, and (iii) the association of the reporting of MD with journal impact factor and CONSORT endorsement status.
Study Design and Setting: Systematic review of palliative care randomized controlled trials. CENTRAL, MEDLINE, and EMBASE (2009e2014) were searched.
Results: One hundred and eight trials (15,560 participants) were included. MD was incompletely reported and not handled in accordance with current guidance. Reporting criteria specified by the CONSORT statement were better reported than those not specified (participant flow, 69%; number of participants not included in the primary outcome analysis, 94%; and the reason for MD, 71%). However, MD in items contributing to scale summaries (10%) and secondary outcomes (9%) were poorly reported, so the proportion of MD stated is likely to be an underestimate. The reason for MD provided was unclear for 54% of participants and only 16% of trials with MD reported a MD sensitivity analysis. The odds of reporting most of the MD and other risk of bias reporting criteria were increased as the journal impact
factor increased and in journals that endorsed the CONSORT statement.
Conclusion: Further development of the CONSORT MD reporting guidance is likely to improve the quality of reporting. Reporting
recommendations are provided
Hydrogel Based Sensors for Biomedical Applications: An Updated Review
Get PDFThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).Biosensors that detect and convert biological reactions to a measurable signal have gained much attention in recent years. Between 1950 and 2017, more than 150,000 papers have been published addressing the applications of biosensors in different industries, but to the best of our knowledge and through careful screening, critical reviews that describe hydrogel based biosensors for biomedical applications are rare. This review discusses the biomedical application of hydrogel based biosensors, based on a search performed through Web of Science Core, PubMed (NLM), and Science Direct online databases for the years 2000–2017. In this review, we consider bioreceptors to be immobilized on hydrogel based biosensors, their advantages and disadvantages, and immobilization techniques. We identify the hydrogels that are most favored for this type of biosensor, as well as the predominant transduction strategies. We explain biomedical applications of hydrogel based biosensors including cell metabolite and pathogen detection, tissue engineering, wound healing, and cancer monitoring, and strategies for small biomolecules such as glucose, lactate, urea, and cholesterol detection are identified. View Full-Tex
Neurotoxicity with persistent unilateral ophthalmoplegia from envenoming by a wild inland taipan (Oxyuranus microlepidotus, Elapidae) in remote outback South Australia
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This author accepted manuscript is made available following 12 month embargo from date of publication (July 2017) in accordance with the publisher’s archiving policyIntroduction: A case of life threatening envenoming by a wild specimen of the inland taipan, Oxyuranus microlepidotus, is described. There have been 11 previously well-documented envenomings by O. microlepidotus, but only 2 were inflicted by wild snakes. Envenomed patients have presented predominantly with defibrinating coagulopathy and neurotoxicity.
Case report: The victim was seeking to observe members of an isolated population of this species and was envenomed while attempting to photograph an approximately 1.5 m specimen. He reported feeling “drowsiness” and blurred vision that progressed to ptosis; he later developed dysphagia and dysarthria. The patient was treated with 1 vial of polyvalent antivenom, which was later followed with an additional two vials of taipan monovalent. He was intubated during retrieval, and recovered after 3 days of intensive care. He had a right ophthalmoplegia that persisted for approximately 1 week post-envenoming. Despite a positive 20-min whole blood clotting test, defibrination coagulopathy was absent, and there was no myotoxicity, or acute kidney injury.
Discussion: Physicians presented with a patient envenomed by O. microlepidotus should remain cognizant of the possible variability of medically important venom toxins in some populations of this species. Some patients seriously envenomed by this species may develop persistent cranial nerve palsies. When clinically indicated, prompt provision of adequate antivenom is the cornerstone of managing O. microlepidotus envenoming. Rapid application of pressure-bandage immobilization and efficient retrieval of victims envenomed in remote locales, preferably by medically well-equipped aircraft, probably improves the likelihood of a positive outcome
Conversion Parkinson’s Disease with Levodopa Abuse and Psychosis
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This author accepted manuscript is made available following 12 month embargo from date of publication (Sept 2017) in accordance with the publisher’s archiving policyConversion disorder (CD) now recognised as functional neurological symptom disorder (DSMV) presents with physical symptoms that are not well explained by organic aetiology. We describe a unique case of Conversion Parkinson’s Disease (PD)