Febuxostat ameliorates methotrexate-induced lung damage

Background: The intention of the present study was to assess the structural affection of the lung following methotrexate (MTX) overdose. The proposed underlying mechanisms involved in lung affection were studied. The possible modulation role of febuxostat over such affection was studied. Materials and methods: Twenty-four rats were divided into three groups: control, MTX-treated, febuxostat-treated. The study was continued for 2 weeks. Lung was processed for histological and immunohistochemical (inducible nitric oxide synthase [iNOS] and cyclooxygenase [COX]-2) studies. Inflammatory markers (tumour necrosis factor alpha [TNF-a], interleukin 1 [IL-1]), Western blot evaluation of nuclear factor kappa B (NF-kB) and oxidative/antioxidative markers were done. Results: Methotrexate-treated group exhibited inflammatory cellular infiltrations, thickened interalveolar septa, dilated congested blood vessels, extravasated blood, and apoptosis. The collagen fibres content increased 3-fold. MTX induced lung affection through oxidative stress (increase MDA/decrease GSH, SOD) and apoptosis. It induced sterile inflammation through an increase of NF-kB (2-fold), IL-1 (3-fold) and TNF-a (3-fold), COX-2 cells (2.5-fold) and iNOS (6-fold). With the use of febuxostat, the normal lung architecture was observed with a bit thickened interalveolar septum and extravasated blood. The collagen fibres content was minimal. Decrement of oxidative stress and sterile inflammation (COX-2 cells and iNOS were comparable to the control group. NF-kB, IL-1 and TNF-a became higher by 34%, 64% and 100%). Conclusions: The overdose of MTX displays inflammatory lung affection with residual fibrosis. It induces lung affection through oxidative stress, apoptosis and sterile inflammation. With the use of febuxostat, the normal lung architecture was preserved with a little structural affection or fibrotic residue. Febuxostat exerts its lung protection through its anti-inflammatory and antioxidant features

Draft Genome Sequence of Photorhabdus luminescens Strain BA1, an Entomopathogenic Bacterium Isolated from Nematodes Found in Egypt

Photorhabdus luminescens strain BA1 is an entomopathogenic bacterium that forms a symbiotic association with Heterorhabditis nematodes. We report here a 5.0-Mbp draft genome sequence for P. luminscens strain BA1, with a G+C content of 42.46% and 4,250 candidate protein-coding genes

Co-administration of Vitamins E and C protects against stress-induced hepatorenal oxidative damage and effectively improves lipid profile at both low and high altitude

The aim of this study was to evaluate the effect of co- administration of vitamins E and C on exhaustive exercise induced-stress in regards to hepatorenal function in rats native to low altitude (LA) and high altitude (HA). In both LA and HA areas, native wistar rats of each area were divided into three groups of 6 rats each, which include stress-free control, forced swimming-induced experimental stress and experimental stress plus vitamins E and C treatment. Lipid profile and Liver and kidney functions were assessed in both groups. HA and LA rats exhibit similar baseline levels of liver and kidney function as well as lipid metabolism profiles. However, HA rats showed decreased levels of antioxidant markers with an increased level of lipid peroxidation. Exhaustive swimming exercise induced a significant increase in the liver and kidney function of rats at both altitudes accompanied with a decrease in antioxidants levels. However, the magnitude of change observed in HA rats was more profound. Also at LA, forced swimming exercise resulted in a significant increase in serum total cholesterol (TChol), triacylglycerides (TAG) and high-density lipoprotein cholesterol (HDL). However, in HA rats, forced swimming exercise caused a significant decrease in serum TChol and low-density lipoprotein (LDL), except for HDL levels which were significantly elevated. Pre- and co-administration of vitamins E and C counteracted the induction of liver and/or kidney function by exhaustive exercise, and lowered TChol and LDL levels in rats at either altitude. In conclusion, at native high altitude: kidney and liver function essentially remained stable; response to stress included more profound oxidative damage to liver and kidney tissues as well as augmented deterioration in lipid metabolism compared to low altitude; and combined administration of vitamins E and C protected against observed oxidative stress damage to liver and kidney tissues and preserved lipid metabolism. At low altitude, combined administration of vitamin E and C protected against stress-induced oxidative damage to the liver and kidney and did preserve normal lipid metabolism, except for HDL. These novel findings reveal the pathophysiological changes in the liver function, kidney function and lipid metabolism occurring at high altitude specifically under stress, and demonstrate the efficacy of combined supplementation of vitamins E and C to normalize these changes.Key words: Exercise, oxidative stress, vitamin E, vitamin C, altitude, rats

Population fluctuations and synanthropy explain transmission risk in rodent-borne zoonoses

Publisher Copyright: © 2022, The Author(s).Population fluctuations are widespread across the animal kingdom, especially in the order Rodentia, which includes many globally important reservoir species for zoonotic pathogens. The implications of these fluctuations for zoonotic spillover remain poorly understood. Here, we report a global empirical analysis of data describing the linkages between habitat use, population fluctuations and zoonotic reservoir status in rodents. Our quantitative synthesis is based on data collated from papers and databases. We show that the magnitude of population fluctuations combined with species’ synanthropy and degree of human exploitation together distinguish most rodent reservoirs at a global scale, a result that was consistent across all pathogen types and pathogen transmission modes. Our spatial analyses identified hotspots of high transmission risk, including regions where reservoir species dominate the rodent community. Beyond rodents, these generalities inform our understanding of how natural and anthropogenic factors interact to increase the risk of zoonotic spillover in a rapidly changing world.Peer reviewe

Draft Genome Sequence of Photorhabdus temperata Strain Meg1, an Entomopathogenic Bacterium Isolated from Heterorhabditis megidis Nematodes

Photorhabdus temperata strain Meg1 is an entomopathogenic bacterium that forms a symbiotic association with Heterorhabditis nematodes. We report here a 4.9-Mbp draft genome sequence for P. temperata strain Meg1, with a G+C content of 43.18% and containing 4,340 candidate protein-coding genes

Recent Advances in Dye Sensitized Solar Cells

Solar energy is an abundant and accessible source of renewable energy available on earth, and many types of photovoltaic (PV) devices like organic, inorganic, and hybrid cells have been developed to harness the energy. PV cells directly convert solar radiation into electricity without affecting the environment. Although silicon based solar cells (inorganic cells) are widely used because of their high efficiency, they are rigid and manufacturing costs are high. Researchers have focused on organic solar cells to overcome these disadvantages. DSSCs comprise a sensitized semiconductor (photoelectrode) and a catalytic electrode (counter electrode) with an electrolyte sandwiched between them and their efficiency depends on many factors. The maximum electrical conversion efficiency of DSSCs attained so far is 11.1%, which is still low for commercial applications. This review examines the working principle, factors affecting the efficiency, and key challenges facing DSSCs

Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: An eco-epidemiological community-based cohort study in Brazil

Background: Zoonotic spillover from animal reservoirs is responsible for a significant global public health burden, but the processes that promote spillover events are poorly understood in complex urban settings. Endemic transmission of Leptospira, the agent of leptospirosis, in marginalised urban communities occurs through human exposure to an environment contaminated by bacteria shed in the urine of the rat reservoir. However, it is unclear to what extent transmission is driven by variation in the distribution of rats or by the dispersal of bacteria in rainwater runoff and overflow from open sewer systems. Methods: We conducted an eco-epidemiological study in a high-risk community in Salvador, Brazil, by prospectively following a cohort of 1401 residents to ascertain serological evidence for leptospiral infections. A concurrent rat ecology study was used to collect information on the fine-scale spatial distribution of 'rattiness', our proxy for rat abundance and exposure of interest. We developed and applied a novel geostatistical framework for joint spatial modelling of multiple indices of disease reservoir abundance and human infection risk. Results: The estimated infection rate was 51.4 (95%CI 40.4, 64.2) infections per 1000 follow-up events. Infection risk increased with age until 30 years of age and was associated with male gender. Rattiness was positively associated with infection risk for residents across the entire study area, but this effect was stronger in higher elevation areas (OR 3.27 95% CI 1.68, 19.07) than in lower elevation areas (OR 1.14 95% CI 1.05, 1.53). Conclusions: These findings suggest that, while frequent flooding events may disperse bacteria in regions of low elevation, environmental risk in higher elevation areas is more localised and directly driven by the distribution of local rat populations. The modelling framework developed may have broad applications in delineating complex animal-environment-human interactions during zoonotic spillover and identifying opportunities for public health intervention

Next Generation Nuclear Plant Methods Technical Program Plan

One of the great challenges of designing and licensing the Very High Temperature Reactor (VHTR) is to confirm that the intended VHTR analysis tools can be used confidently to make decisions and to assure all that the reactor systems are safe and meet the performance objectives of the Generation IV Program. The research and development (R&D) projects defined in the Next Generation Nuclear Plant (NGNP) Design Methods Development and Validation Program will ensure that the tools used to perform the required calculations and analyses can be trusted. The Methods R&D tasks are designed to ensure that the calculational envelope of the tools used to analyze the VHTR reactor systems encompasses, or is larger than, the operational and transient envelope of the VHTR itself. The Methods R&D focuses on the development of tools to assess the neutronic and thermal fluid behavior of the plant. The fuel behavior and fission product transport models are discussed in the Advanced Gas Reactor (AGR) program plan. Various stress analysis and mechanical design tools will also need to be developed and validated and will ultimately also be included in the Methods R&D Program Plan. The calculational envelope of the neutronics and thermal-fluids software tools intended to be used on the NGNP is defined by the scenarios and phenomena that these tools can calculate with confidence. The software tools can only be used confidently when the results they produce have been shown to be in reasonable agreement with first-principle results, thought-problems, and data that describe the “highly ranked” phenomena inherent in all operational conditions and important accident scenarios for the VHTR

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects.Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD.Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3 weeks study period.Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858–2.214; 1.300, 95% CI: 1.086–1.514 and 4.200, 95% CI: 3.321–5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = −2.000, 95% CI: −2.651 to −1.349; Median difference = 1.000, 95% CI: 0.3489–1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3–4 days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05).Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone.Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618

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