Deciphering metal-induced oxidative damages on glycated albumin structure and function

Background: Metal ions such as copper or zinc are involved in the development of neurodegenerative pathologies and metabolic diseases such as diabetes mellitus. Albumin structure and functions are impaired following metal- and glucose-mediated oxidative alterations. The aim of this study was to elucidate effects of Cu(II) and Zn(II) ions on glucose-induced modifications in albumin by focusing on glycation, aggregation, oxidation and functional aspects. Methods: Aggregation and conformational changes in albumin were monitored by spectroscopy, fluorescence and microscopy techniques. Biochemical assays such as carbonyl, thiol groups, albumin-bound Cu, fructosamine and amine group measurements were used. Cellular assays were used to gain functional information concerning antioxidant activity of oxidized albumins. Results: Both metals promoted inhibition of albumin glycation associated with an enhanced aggregation and oxidation process. Metal ions gave rise to the formation of β-amyloid type aggregates in albumin exhibiting impaired antioxidant properties and toxic activity to murine microglia cells (BV2). The differential efficiency of both metal ions to inhibit albumin glycation, to promote aggregation and to affect cellular physiology is compared. Conclusions and general significance: Considering the key role of oxidized protein in pathology complications, glycation-mediated and metal ion-induced impairment of albumin properties might be important parameters to be followed and fought. © 2013 Elsevier B.V

Fault Growth and Propagation During Incipient Continental Rifting: Insights from a Combined Aeromagnetic and Shuttle Radar Topography Mission Digital Elevation Model Investigation of the Okavango Rift Zone, Northwest Botswana

Digital Elevation Models (DEM) extracted from the Shuttle Radar Topography Mission (SRTM) data and high-resolution aeromagnetic data are used to characterize the growth and propagation of faults associated with the early stages of continental extension in the Okavango Rift Zone (ORZ), northwest Botswana. Significant differences in the height of fault scarps and the throws across the faults in the basement indicate extended fault histories accompanied by sediment accumulation within the rift graben. Faults in the center of the rift either lack topographic expressions or are interpreted to have become inactive, or have large throws and small scarp heights indicating waning activity. Faults on the outer margins of the rift exhibit either (1) large throws or significant scarp heights and are considered older and active or (2) throws and scarp heights that are in closer agreement and are considered young and active. Fault linkages between major fault systems through a process of fault piracy have combined to establish an immature border fault for the ORZ. Thus, in addition to growing in length (by along-axis linkage of segments), the rift is also growing in width (by transferring motion to younger faults along the outer margins while abandoning older faults in the middle). Finally, utilization of preexisting zones of weakness allowed the development of very long faults (\u3e100 km) at a very early stage of continental rifting, explaining the apparent paradox between the fault length versus throw for this young rift. This study clearly demonstrates that the integration of the SRTM DEM and aeromagnetic data provides a 3-D view of the faults and fault systems, providing new insight into fault growth and propagation during the nascent stages of continental rifting

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-gamma transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm(2) to 475/mm(2) in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3 alpha and PPAR coactivator-1 alpha (PGC-1 alpha) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis. Copyright (C) 2012 S. Karger AG, Base

Enjeux et défis de la mise en oeuvre des Unités Forestières Artisanales dans le Maï-Ndombe en République Démocratique du Congo

peer reviewedL’exploitation forestière artisanale représente à la fois un enjeu et un défi majeurs dans l’optique d’une gestion durable et légale des forêts en République Démocratique du Congo (RDC). Bien qu’elle constitue un potentiel économique important, le secteur demeure cependant dans le domaine informel et illégal, en raison notamment des lacunes juridiques. Pour tenter de le réguler, les arrêtés n°84/2016 du 29 octobre 2016 relatif à l’exploitation forestière et n°85/2016, qui institutionnalise l’Unité Forestière Artisanale (UFA), ont été édictés par le Ministère de l’Environnement. La présente étude, conduite dans la Province de Maï-Ndombe entre janvier et février 2018, décrit les perceptions des parties prenantes sur l’applicabilité de ces textes et les défis de mise en oeuvre des UFA dans cette région. Des enquêtes ont été réalisées essentiellement avec l’administration forestière, les autorités politico-administratives et les exploitants artisanaux. L’analyse qualitative des données recueillies a permis d’établir des convergences ou divergences entre les déclarations des différents acteurs. Les résultats montrent que les textes régissant le secteur du sciage artisanal sont peu connus et/ou non respectés par les acteurs sur le terrain. Les exploitants accèdent à la profession sans détenir au préalable les documents administratifs requis. La licence d’abattage est utilisée à la place du permis de coupe artisanal et le carnet ou registre d’exploitation n’est tenu pour aucune opération forestière. Les souches des arbres abattus ou les billes ne comportent aucun marquage, rendant impossible une quelconque traçabilité. En outre, les différents acteurs n’ont pas les compétences techniques, financières et matérielles adéquates pour gérer une UFA. Cette étude révèle donc que, quatre années après l’instauration des UFA, rien n’est effectif sur le terrain. La mise en oeuvre de ce dispositif demeure un défi opérationnel en RDC. Le risque d’une réglementation « coquille creuse » est grand malgré le caractère non durable de l’exploitation du bois. Un renforcement des capacités des acteurs clés apparaît indispensable pour rendre effectif ce nouveau mode de gestion des forêts.Artisanal logging represents both a major issue and a major challenge for sustainable and legal forest management in the Democratic Republic of Congo (DRC). Although it has significant economic potential, the sector remains informal and illegal, mainly due to legal loopholes. In an attempt to regulate it, decrees no. 84/2016 of October 29, 2016 on logging, and no. 85/2016, which institutionalizes the Artisanal Forest Unit (AFU), was issued by the Ministry of the Environment. This study, conducted in the Province of Maï-Ndombe in February 2018, describes the perceptions of stakeholders on the applicability of these texts and the challenges of implementing AFUs in this region. Surveys were conducted primarily with the forestry administration, political-administrative authorities and artisanal loggers. The qualitative analysis of the data collected made it possible to establish convergences or divergences between the statements of the various actors. The results show that the texts governing the artisanal sawmilling sector are little known and/or not respected by the actors in the field. Operators enter the profession without first having the required administrative documents. The felling license is used instead of the artisanal cutting permit, and the logbook or logging register is not kept for any forestry operation. The stumps of felled trees or logs are not marked, making traceability impossible. In addition, the various actors do not have the technical, financial and material skills required to manage an AFU. This study therefore reveals that, four years after the establishment of AFUs, nothing is effective on the ground. The implementation of this system thus remains a major operational challenge in the DRC. The risk of a "hollow shell" regulation is high despite the unsustainable nature of timber exploitation. Capacity building of key actors appears to be essential to make this new forest management method effective

Implementation research of a cluster randomized trial evaluating the implementation and effectiveness of intermittent preventive treatment for malaria using dihydroartemisinin-piperaquine on reducing malaria burden in school-aged children in Tanzania: methodology, challenges, and mitigation

BACKGROUND: It has been more than 20 years since the malaria epidemiologic shift to school-aged children was noted. In the meantime, school-aged children (5-15 years) have become increasingly more vulnerable with asymptomatic malaria prevalence reaching up to 70%, making them reservoirs for subsequent transmission of malaria in the endemic communities. Intermittent Preventive Treatment of malaria in schoolchildren (IPTsc) has proven to be an effective tool to shrink this reservoir. As of 3(rd) June 2022, the World Health Organization recommends IPTsc in moderate and high endemic areas. Even so, for decision-makers, the adoption of scientific research recommendations has been stifled by real-world implementation challenges. This study presents methodology, challenges faced, and mitigations used in the evaluation of the implementation of IPTsc using dihydroartemisinin-piperaquine (DP) in three councils (Handeni District Council (DC), Handeni Town Council (TC) and Kilindi DC) of Tanga Region, Tanzania so as to understand the operational feasibility and effectiveness of IPTsc on malaria parasitaemia and clinical malaria incidence. METHODS: The study deployed an effectiveness-implementation hybrid design to assess feasibility and effectiveness of IPTsc using DP, the interventional drug, against standard of care (control). Wards in the three study councils were the randomization unit (clusters). Each ward was randomized to implement IPTsc or not (control). In all wards in the IPTsc arm, DP was given to schoolchildren three times a year in four-month intervals. In each council, 24 randomly selected wards (12 per study arm, one school per ward) were chosen as representatives for intervention impact evaluation. Mixed design methods were used to assess the feasibility and acceptability of implementing IPTsc as part of a more comprehensive health package for schoolchildren. The study reimagined an existing school health programme for Neglected Tropical Diseases (NTD) control include IPTsc implementation. RESULTS: The study shows IPTsc can feasibly be implemented by integrating it into existing school health and education systems, paving the way for sustainable programme adoption in a cost-effective manner. CONCLUSIONS: Through this article other interested countries may realise a feasible plan for IPTsc implementation. Mitigation to any challenge can be customized based on local circumstances without jeopardising the gains expected from an IPTsc programme. Trial registration clinicaltrials.gov, NCT04245033. Registered 28 January 2020, https://clinicaltrials.gov/ct2/show/NCT04245033

Feature extraction and selection for Arabic tweets authorship authentication

© 2017, Springer-Verlag Berlin Heidelberg. In tweet authentication, we are concerned with correctly attributing a tweet to its true author based on its textual content. The more general problem of authenticating long documents has been studied before and the most common approach relies on the intuitive idea that each author has a unique style that can be captured using stylometric features (SF). Inspired by the success of modern automatic document classification problem, some researchers followed the Bag-Of-Words (BOW) approach for authenticating long documents. In this work, we consider both approaches and their application on authenticating tweets, which represent additional challenges due to the limitation in their sizes. We focus on the Arabic language due to its importance and the scarcity of works related on it. We create different sets of features from both approaches and compare the performance of different classifiers using them. We experiment with various feature selection techniques in order to extract the most discriminating features. To the best of our knowledge, this is the first study of its kind to combine these different sets of features for authorship analysis of Arabic tweets. The results show that combining all the feature sets we compute yields the best results

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes</p> <p>Methods</p> <p>Cohort analysis comparing patients treated under the PCT strategy (registered April-September 2006) with patients treated under health-facility-based DOT (registered April-September 2005). The primary outcome was the cure rate. Differences were assessed by calculating the risk ratios. Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression.</p> <p>Results</p> <p>In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort. There was no significant difference in cure rates between the cohorts (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.16). In the PCT cohort, significantly more patients had successful treatment (cure or treatment completed; RR: 1.10; 95%CI: 1.01-1.15). There were no characteristics of supporters that were associated with treatment outcome.</p> <p>Conclusion</p> <p>The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT. The results indicate that there are no specific prerequisites for the supporter chosen by the patient. The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility.</p