Harnessing inter-disciplinary collaboration to improve emergency care in low- and middle-income countries (LMICs): results of research prioritisation setting exercise

Background More than half of deaths in low- and middle-income countries (LMICs) result from conditions that could be treated with emergency care - an integral component of universal health coverage (UHC) - through timely access to lifesaving interventions. Methods The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings. Results The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care – all within LMICs. Conclusions Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities

Effects of Precursor Concentration and Acidic Sulfate in Aqueous Glyoxal−OH Radical Oxidation and Implications for Secondary Organic Aerosol

Previous experiments demonstrated that aqueous OH radical oxidation of glyoxal yields low-volatility compounds. When this chemistry takes place in clouds and fogs, followed by droplet evaporation (or if it occurs in aerosol water), the products are expected to remain partially in the particle phase, forming secondary organic aerosol (SOA). Acidic sulfate exists ubiquitously in atmospheric water and has been shown to enhance SOA formation through aerosol phase reactions. In this work, we investigate how starting concentrations of glyoxal (30−3000 μM) and the presence of acidic sulfate (0−840 μM) affect product formation in the aqueous reaction between glyoxal and OH radical. The oxalic acid yield decreased with increasing precursor concentrations, and the presence of sulfuric acid did not alter oxalic acid concentrations significantly. A dilute aqueous chemistry model successfully reproduced oxalic acid concentrations, when the experiment was performed at cloud-relevant concentrations (glyoxal <300 μM), but predictions deviated from measurements at increasing concentrations. Results elucidate similarities and differences in aqueous glyoxal chemistry in clouds and in wet aerosols. They validate for the first time the accuracy of model predictions at cloud-relevant concentrations. These results suggest that cloud processing of glyoxal could be an important source of SOA

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets

Magnetoliposome for alendronate delivery

1 - ArticleEncapsulation into liposomes has been developed in order to allow protection of therapeutical agents against enzymatic degradation, and to reduce doses and toxic side effects. Selective, targeted and controlled release of the drug out of the lipid vesicle is still, however, difficult to achieve. Meanwhile, thanks to their magnetic properties, superparamagnetic iron oxide (SPIO) nanoparticles have also been considered as good delivery vehicles after grafting a therapeutic drug on their surface. A combination of both properties (magnetic targeting and drug encapsulation) is evaluated to deliver an anticancer drug : alendronate, an hydroxymethylene bisphosphonate molecule. gamma-Fe(2)O(3) nanocrystals grafted with alendronate were tested with or without liposome encapsulation, with and without magnetic field, on three human cancer cell lines, MDA-MB231, A431 and U87-MG. Cytotoxicity was measured as well as drug internalization. While results were not identical on the three cell lines with the different formulations, an effective 100% cytotoxic effect could only be achieved with alendronate grafted-SPIO entrapped into liposomes and exposed to a magnetic field

In vitro assessment of liposomal neridronate on MDA-MB-231 human breast cancer cells

1 - ArticleBisphosphonates have been used for decades in the standard therapy of bone-related diseases, including bone metastasis of various malignancies, and they might as well be toxic on early cancer cells themselves. In order to allow a better delivery of neridronate (a N-containing bisphosphonate with relatively poor activity), liposomes were evaluated in vitro on cancer cell lines (MDA-MB 231, U87-MG and Caco2). After chemical synthesis, this water-soluble molecule was encapsulated into liposomes containing DOPC:DOPG:Chol (72:27:1 molar ratio). The influence of neridronate (free or liposomal) on cell viability or proliferation after treatment was evaluated using the MTT method, as well as cell migration and invasion assays; these techniques showed a drastic improvement of the action of neridronate on MDA-MB-231 cells with an EC50 fifty times lower when neridronate was encapsulated. Internalization of liposomes was followed by flow cytometry and fluorescence microscopy, demonstrating internalization via the endocytic pathway. Furthermore, since over-expression of matrix metalloproteinases (particularly MMP-2 and MMP-9) has been correlated to poor prognosis in many cancer types, detection of MMP expression is a satisfactory indication of the therapy efficiency and was then performed on treated cells. On MDA-MB-231 cells, MPPs expression was also significantly reduced by neridronate while entrapped in liposomes

Granulomatose avec polyangéite du sujet âgé: à propos de deux cas et revue de la littérature

La granulomatose avec polyangéite (GPA) est une vascularite nécrosante des vaisseaux de petit calibre. L'âge moyen d'entrée dans la GPA est entre 35 et 55 ans, les formes gériatriques sont cependant rares, Nous rapportons deux cas de GPA révélés après 60 ans, le mode de révélation était inhabituel, ophtalmologique dans le premier cas et cutané dans le deuxième cas

New multimodal iron oxide nanoparticles as nanotools for cancer

9 - Conference Paper: NSTI Nanotech 2010: Bio Sensors, Instruments, Medical, Environment and Energy, 21-24 juin 2010, Anaheim (USA)The goal of this project is to elaborate new multifunctional magnetic nanovectors to vectorize biological interest molecules for therapy and diagnostic applications. Indeed, iron oxide nanoparticles, tanks to their magnetic properties, are used as contrast agents for MRI. Moreover the specific surface coating by interest molecules permit to consider them as a drug delivery vehicle for therapeutic molecules. Liposomes are also considering as good candidates for drug delivery systems. Indeed, lipid vesicle encapsulation allows protection of the agent against enzymatic degradation, and reduces the dose and toxics effects. However, the selective and controlled release of the drug out of the vesicles is still difficult to master, especially at cell and tissue levels. This can be achieved by magnetic targeting. Recent studies have shown that in addition to inhibit bone resorption, Hydroxymethylene Bisphosphonates molecules present anti-tumour properties in variety of cancer. However, these properties can not be exploited due to their very high affinity to bone. In order to overcome this problem, we use two strategies. The first one is the vectorization trough iron oxide nanocrystal surface functionalization. The second one was to use superparamagnetic liposomes

Mertensene, a halogenated monoterpene, induces G2/M cell cycle arrest and caspase dependent apoptosis of human colon adenocarcinoma HT29 cell line through the modulation of ERK-1/-2, AKT and NF-κB signaling

Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S.G. Gmelin) Santelices and Hommersand and we highlight its inhibitory effect on the viability of two human colorectal adenocarcinoma cell lines HT29 and LS174. Interestingly, exposure of HT29 cells to different concentrations of mertensene correlated with the activation of MAPK ERK-1/-2, Akt and NF-κB pathways. Moreover, mertensene-induced G2/M cell cycle arrest was associated with a decrease in the phosphorylated forms of the anti-tumor transcription factor p53, retinoblastoma protein (Rb), cdc2 and chkp2. Indeed, a reduction of the cellular level of cyclin-dependent kinases CDK2 and CDK4 was observed in mertensene-treated cells. We also demonstrated that mertensene triggers a caspase-dependent apoptosis in HT29 cancer cells characterized by the activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Besides, the level of death receptor-associated protein TRADD increased significantly in a concentration-dependent manner. Taken together, these results demonstrate the potential of mertensene as a drug candidate for the treatment of colon cancer. © 2017 by the authors. Licensee MDPI