Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists

Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK

Effect of changes in climate and emissions on future sulfate-nitrate-ammonium aerosol levels in the United States

Global simulations of sulfate, nitrate, and ammonium aerosols are performed for the present day and 2050 using the chemical transport model GEOS-Chem. Changes in climate and emissions projected by the IPCC A1B scenario are imposed separately and together, with the primary focus of the work on future inorganic aerosol levels over the United States. Climate change alone is predicted to lead to decreases in levels of sulfate and ammonium in the southeast U.S. but increases in the Midwest and northeast U.S. Nitrate concentrations are projected to decrease across the U.S. as a result of climate change alone. In the U.S., climate change alone can cause changes in annually averaged sulfate-nitrate-ammonium of up to 0.61 μg/m^3, with seasonal changes often being much larger in magnitude. When changes in anthropogenic emissions are considered (with or without changes in climate), domestic sulfate concentrations are projected to decrease because of sulfur dioxide emission reductions, and nitrate concentrations are predicted to generally increase because of higher ammonia emissions combined with decreases in sulfate despite reductions in emissions of nitrogen oxides. The ammonium burden is projected to increase from 0.24 to 0.36 Tg, and the sulfate burden to increase from 0.28 to 0.40 Tg S as a result of globally higher ammonia and sulfate emissions in the future. The global nitrate burden is predicted to remain essentially constant at 0.35 Tg, with changes in both emissions and climate as a result of the competing effects of higher precursor emissions and increased temperature

Systems Immunology Analysis Reveals an Immunomodulatory Effect of Snail-p53 Binding on Neutrophil- and T Cell-Mediated Immunity in KRAS Mutant Non-Small Cell Lung Cancer

Immunomodulation and chronic inflammation are important mechanisms utilized by cancer cells to evade the immune defense and promote tumor progression. Therefore, various efforts were focused on the development of approaches to reprogram the immune response to increase the immune detection of cancer cells and enhance patient response to various types of therapy. A number of regulatory proteins were investigated and proposed as potential targets for immunomodulatory therapeutic approaches including p53 and Snail. In this study, we investigated the immunomodulatory effect of disrupting Snail-p53 binding induced by the oncogenic KRAS to suppress p53 signaling. We analyzed the transcriptomic profile mediated by Snail-p53 binding inhibitor GN25 in non-small cell lung cancer cells (A549) using Next generation whole RNA-sequencing. Notably, we observed a significant enrichment in transcripts involved in immune response pathways especially those contributing to neutrophil (IL8) and T-cell mediated immunity (BCL6, and CD81). Moreover, transcripts associated with NF-κB signaling were also enriched which may play an important role in the immunomodulatory effect of Snail-p53 binding. Further analysis revealed that the immune expression signature of GN25 overlaps with the signature of other therapeutic compounds known to exhibit immunomodulatory effects validating the immunomodulatory potential of targeting Snail-p53 binding. The effects of GN25 on the immune response pathways suggest that targeting Snail-p53 binding might be a potentially effective therapeutic strategy

Reducing anemia prevalence in Afghanistan: socioeconomic correlates and the particular role of agricultural assets

This research aims to examine the socio-economic correlates of anemia in women, and potential sources of iron in household diets in Afghanistan. It also examines whether ownership of agricultural (particularly livestock) assets and their use in food production has a role in alleviating anaemia, especially where local markets may be inadequate. We analyse data from the 2010/11 Afghanistan Multiple Indicator Cluster Survey, estimating a logistic regression to examine how anemia status of women is associated with socio-economic covariates. A key result found is that sheep ownership has a protective effect in reducing anemia (prevalence odds ratio of sheep ownership on anemia of 0.83, 95% confidence interval (CI): 0.73–0.94) after controlling for wealth and other covariates. This association is found to be robust to alternative model specifications. Given the central role of red meat in heme iron provision and absorption of non-heme iron, we hypothesise that sheep ownership promotes mutton consumption from own-production in a setting where market-sourced provision of nutritious food is a challenge. We then use the 2011/12 National Risk and Vulnerability Assessment household data to understand the Afghan diet from the perspective of dietary iron provision, and to understand interactions between own-production, market sourcing and mutton consumption. Sheep ownership is found to increase the likelihood that a household consumed mutton (odds ratio of 1.27, 95% CI: 1.15–1.42), the number of days in the week that mutton was consumed (prevalence rate ratio of 1.24. 95% CI: 1.12–1.37) and the quantity of mutton consumed (7 grams/person/week). In the subsample of mutton consumers, households sourcing mutton mostly from own production consumed mutton 1.5 days more frequently on average than households relying on market purchase, resulting in 100 grams per person per week higher mutton intake. Thus this analysis lends support to the notion that the linkage between sheep ownership and anemia risk is at least partly due to consumption arising from own-production in the presence of market incompleteness

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

IL-17 Induced Autophagy Regulates Mitochondrial Dysfunction and Fibrosis in Severe Asthmatic Bronchial Fibroblasts

The accumulation of fibroblasts, their synthesis of extracellular matrix (ECM) proteins and their innate resistance to apoptosis are characteristics of subepithelial fibrosis observed in severe asthma. Interleukin-17 (IL-17) is an important regulator of airway remodeling in asthma. However, the contribution of IL-17 to the pro-fibrotic phenotype of bronchial fibroblasts is not well-characterized. In this study, we investigated whether IL-17 induced autophagy regulates mitochondrial and pro-fibrotic function in bronchial fibroblasts. The primary cultured bronchial fibroblasts isolated from non-asthmatic (NHBF) and severe asthmatic (DHBF) subjects were treated with IL-17 in order to ascertain its effect on mitochondrial function, mitochondrial quality control, and apoptosis using immunoblotting and flow cytometric analyses. At baseline, DHBF exhibited higher levels of mitophagy and mitochondrial biogenesis compared to NHBF. Immunohistochemical evaluation of bronchial biopsies showed intense PINK1 immunoreactivity in severe asthma than in control. IL-17 intensified the mitochondrial dysfunction and impaired the mitochondrial quality control machinery in NHBF and DHBF. Moreover, IL-17 augmented a pro-fibrotic and anti-apoptotic response in both group of fibroblasts. Inhibition of autophagy using bafilomycin-A1 reduced PINK1 expression in NHBF and restored the IL-17 mediated changes in PINK1 to their basal levels in DHBF. Bafilomycin-A1 also reversed the IL-17 associated fibrotic response in these fibroblasts, suggesting a role for IL-17 induced autophagy in the induction of fibrosis in bronchial fibroblasts. Taken together, our findings suggest that IL-17 induced autophagy promotes mitochondrial dysfunction and fibrosis in bronchial fibroblasts from both non-asthmatic and severe asthmatic subjects. Our study provides insights into the therapeutic potential of targeting autophagy in ameliorating fibrosis, particularly in severe asthmatic individuals

Exploring CRM effectiveness: an institutional theory perspective

This study identifies the potential contribution that institutional theory can make to understanding the success of marketing practices. Based on institutional theory, we argue that the effectiveness of marketing practices decreases when firms are motivated to adopt such practices under the influence of institutional pressures originating in firms' environments. However, alignment between a practice and a firm's marketing strategy may buffer against these negative effects. We apply these insights to the case of customer relationship management (CRM). CRM is considered an important way to enhance customer loyalty and firm performance, but it has also been criticized for being expensive and for not living up to expectations. Empirical data from 107 organizations confirm that, in general, adopting CRM for mimetic motives is likely to result in fewer customer insights as a result of using this practice. Our study suggests that institutional theory has much to offer to the investigation of the effectiveness of marketing practices

Forecasting urban water demand using different hybrid-based metaheuristic algorithms’ inspire for extracting artificial neural network hyperparameters

This research offers a novel methodology for quantifying water needs by assessing weather variables, applying a combination of data preprocessing approaches, and an artificial neural network (ANN) that integrates using a genetic algorithm enabled particle swarm optimisation (PSOGA) algorithm. The PSOGA performance was compared with different hybrid-based metaheuristic algorithms’ behaviour, modified PSO, and PSO as benchmarking techniques. Based on the findings, it is possible to enhance the standard of initial data and select optimal predictions that drive urban water demand through effective data processing. Each model performed adequately in simulating the fundamental dynamics of monthly urban water demand as it relates to meteorological variables, proving that they were all successful. Statistical fitness measures showed that PSOGA-ANN outperformed competing algorithms

Targeting AnxA1/Fpr2/ALX Regulates Neutrophil Function Promoting Thrombo-Inflammation Resolution in Sickle Cell Disease

NIH/NHLBI (HL134959-01A1 [FNEG]; HL098435, HL133497, HL141155, and GM12130 [AWO]; HL142604 [RP]), the AHA (19PRE34380751 [ZAY]) and the Royal Society Wolfson Foundation (RSWF\R3\183001 [FNEG])