1,540 research outputs found

    Smart DC Grid integration in railway systems

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    International audienceCet article prĂ©sente une nouvelle solution Ă©cologique pour rĂ©cupĂ©rer l'Ă©nergie de freinage des trains par l'intĂ©gration d'un Smart DC micro-grid dans les systĂšmes ferroviaires. Le principe est de stocker l'excĂšs de l'Ă©nergie de freinage dans un systĂšme de stockage hybride afin de le rĂ©utiliser pour alimenter d'autres applications non-ferroviaires qui pourraient ĂȘtre installĂ©es dans la station oĂč Ă  proximitĂ©, ce qui va amĂ©liorer l'efficacitĂ© Ă©nergĂ©tique globale du systĂšme. This paper introduces a new green solution to recover trains braking energy by integrating Smart DC micro-grid concept in railway systems. It is based on storing the excess of braking energy in a hybrid storage system and re-using it in non-railway applications such as auxiliary loads in a station or in proximity, which will increase the total energy efficiency.</p

    FORMULATION AND EVALUATION OF ATORVASTATIN CALCIUM NANOCRYSTALS CONTAINING P-GLYCOPROTEIN INHIBITORS FOR ENHANCING ORAL DELIVERY

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    Objective: The main objective of this study was to develop atorvastatin calcium (ATR) as an oral drug delivery system for a P-glycoprotein (P-gp) substrate drug using different pharmaceutical excipients that inhibit P-glycoprotein and evaluate the influence of nanocrystals on the dissolution characteristics and bioavailability compared to the plain drug. Methods: A nanosuspension was prepared by Solvent-antisolvent precipitation method using a solvent containing stabilizer that act as a p-gp inhibitor dissolved in distilled water as polyethylene glycol 300, polyethylene glycol 400 (PEG 300, PEG 400), tween 20 and tween 80 while the solvent selected for atorvastatin calcium was methanol. The concentrations were as follows: PEG 300 and 400 = 0.25% w/v, tween 20 and 80 = 0.75% v/v. Nanocrystals were extracted from the suspension and characterized. Results: Particle size of the drug was 1307±127.79 nm while the formulas prepared ranged from 223±17.67 to 887±58.12 nm. Pure ATR had a saturated solubility of 0.059±0.005 mg/ml and the prepared nanocrystals ranged from 0.32±0.021 to 0.88±0.019 mg/ml. The Percentage of drug released of plain atorvastatin calcium reached 41.49% while the formula ranged from 44.32 to 61.5%. Both XRD and SEM discussed the degree of crystallinity as follows: F1&lt;F2&lt;F4&lt;F3&lt;ATR. Conclusion: 0.3% of PEG 300 and PEG 400 were not enough to formulate proper nanocrystals while 0.75% tween 20 and tween 80 achieved acceptable formulas. F4 which is prepared with tween 80 exhibited the highest enhancement in saturated solubility, dissolution rate and subsequently expected to have improved oral bioavailability

    Nanocarriers for simultaneous delivery of structurally different polynucleotides encoding antigens and adjuvants

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    The rapid approval of mRNA-based vaccines for human use following the Covid-19 pandemic established their public health value. Yet, room for improvement to reduce number of required booster doses still exists. This study aimed to investigate the development of a nanocarrier to co-deliver NA-encoded antigens and adjuvants and achieve their time-resolved expression, such that adjuvant expression follows target cell (APC) priming with antigen expression. Hence, a core-shell system was constructed based on a plasmid DNA (pDNA)-gelatin coacervate core, thermally stabilized into a nanogel, coated with protamine (P-TS-CoAc), and surface loaded with mRNA. The system showed unique co-transfectional ability for two such NAs encoding fluorescent reporter proteins when compared to several established controls in dendritic murine cell line (DC2.4). The system also showed time-resolved expression of the two NAs, with a rapid and transient expression of mRNA on the shell and a delayed, prolonged-expression of pDNA in the core. NA-encoded adjuvant candidates were selected to assess P-TS-CoAc’s capacity to transfect them into DC2.4, namely, CCL4 and CCR7, involved in mobilizing immune cells towards inflammation sites or draining lymph nodes, respectively. CCL4 encoding NAs induced CCL4 release from DC2.4 following electroporation, yet, not upon DC2.4 treatment with P-TS-CoAc loaded with CCL4 encoding-NAs. Further studies could still be conducted to improve system performance.Die rasche Zulassung von mRNA-basierten Impfstoffen fĂŒr den menschlichen Gebrauch nach der Covid-19-Pandemie hat ihren Wert fĂŒr die öffentliche Gesundheit bewiesen. Dennoch gibt es Raum fĂŒr Verbesserungen, um die Anzahl der erforderlichen Auffrischungsdosen zu verringern. Ziel dieser Studie war es, einen NanotrĂ€ger zu entwickeln, der Nukleotid (NT)-kodierte Antigene und Adjuvantien gemeinsam abgibt und deren zeitversetzte Expression ermöglicht, so dass die Adjuvantexpression dem Priming der Zielzellen (APC) mit der Antigenexpression folgt. Daher wurde ein Kern-Schale-System konstruiert, das auf einem Plasmid-DNA (pDNA)- Gelatine-Koazervat-Kern basiert, der thermisch zu einem Nanogel stabilisiert, mit Protamin (P-TS-CoAc) beschichtet und an der OberflĂ€che mit mRNA beladen wurde. Das System zeigte eine einzigartige Co-Transfektion fĂŒr beide NT, die fĂŒr fluoreszierende Reporterproteine kodieren, im Vergleich zu mehreren etablierten Kontrollen in einer dendritischen MĂ€usezelllinie (DC2.4). Ebenso zeigte das System eine zeitversetzte Expression der beiden NT, mit einer schnellen,vorĂŒbergehenden Expression der mRNA und einer verzögerten, lĂ€ngeren Expression der pDNA. Es wurden NT-kodierte Adjuvans-Kandidaten ausgewĂ€hlt, um die TransfektionsfĂ€higkeit von P-TS-CoAc in DC2.4 zu prĂŒfen. Diese waren CCL4 und CCR7, die an der Mobilisierung von Immunzellen zu EntzĂŒndungsherden bzw. drainierenden Lymphknoten beteiligt sind. CCL4-kodierende NT induzierten die Freisetzung von CCL4 aus DC2.4 nach Elektroporation, jedoch nicht nach Behandlung von DC2.4 mit entsprechend beladenen PTS- CoAc. Weitere Studien könnten durchgefĂŒhrt werden, um die Leistung des Systems zu verbessern

    Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems

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    Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin–pDNA coacervate in its center. Thermal stabilization enhances the core’s colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications

    Doubt m-Polar Fuzzy Sets Based on BCK-Algebras

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    Doubt m-polar subalgebras (ideals) were introduced and some properties were investigated. Also, doubt m-polar positive implicative (commutative) ideals were defined and related results were proved

    Comparison of routine health management information system versus enhanced inpatient malaria surveillance for estimating the burden of malaria among children admitted to four hospitals in Uganda.

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    The primary source of malaria surveillance data in Uganda is the Health Management Information System (HMIS), which does not require laboratory confirmation of reported malaria cases. To improve data quality, an enhanced inpatient malaria surveillance system (EIMSS) was implemented with emphasis on malaria testing of all children admitted in select hospitals. Data were compared between the HMIS and the EIMSS at four hospitals over a period of 12 months. After the implementation of the EIMSS, over 96% of admitted children under 5 years of age underwent laboratory testing for malaria. The HMIS significantly overreported the proportion of children under 5 years of age admitted with malaria (average absolute difference = 19%, range = 8-27% across the four hospitals) compared with the EIMSS. To improve the quality of the HMIS data for malaria surveillance, the National Malaria Control Program should, in addition to increasing malaria testing rates, focus on linking laboratory test results to reported malaria cases

    Characterization, antibacterial, antioxidant, antidiabetic, and anti-inflammatory activities of green synthesized silver nanoparticles using Phragmanthera austroarabica A. G. Mill and J. A. Nyberg extract

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    IntroductionDiabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.MethodsThe plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.Results and DiscussionThe results showed a decrease in body fat, obesity, an improvement in lipid profiles, normalization of hyperglycemia, insulin resistance, and hyperinsulinemia, and an improvement in liver tissue structure and function. However, the results obtained from AgNPs for both extract and the pure gallic acid were better in most measured parameters. Additionally, the activity of both the crude extract of the plant and its AgNPs were evaluated against a number of gram-positive, gram-negative bacteria and fungi. Although the activity of the crude extract ranged from moderate to weak or even non-active, the AgNPs of the plant extract clearly enhanced the antimicrobial activity. AgNPs of the extract demonstrated remarkable activity, especially against the Gram-negative pathogens Proteus vulgaris (MIC 2.5 ÎŒg/ml) and Pseudomonas aeruginosa (MIC 5 ÎŒg/ml). Furthermore, a promising antimicrobial activity was shown against the Gram-positive pathogen Streptococcus mutants (MIC 1.25 ÎŒg/ml)

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

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    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

    Post-vasectomy semen analysis: Optimizing laboratory procedures and test interpretation through a clinical audit and global survey of practices

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    Purpose: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and Methods: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic’s Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA’s. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy.American Center for Reproductive Medicin

    The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

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    Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients
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