Preoperative assessment of cardiovascular risk in patients undergoing noncardiac surgery: The Orion study

In patients undergoing noncardiac surgery risk indices can estimate patients' perioperative risk of major cardiovascular complications. The indexes currently in use were derived from observational studies that are now outdated with respect to the current clinical context. We undertook a prospective, observational, cohort study to derive, validate, and compare a new risk index with established risk indices. We evaluated 7335 patients (mean age 63±13 years) who underwent noncardiac surgery. Based on prospective data analysis of 4600 patients (derivation cohort) we developed an Updated Cardiac Risk Score (UCRS), and validated the risk score on 2735 patients (validation cohort). Four variables (i.e. the UCRS) were significantly associated with the risk of a major perioperative cardiovascular events: high-risk surgery, preoperative estimate glomerular filtration rate <30 ml/min/1.73 m2, age ≥75 years, and history of heart failure. Based on the UCRS we created risk classes 1,2,3 and 4 and their corresponding 30-day risk of a major cardiovascular complication was 0.8% (95% confidence interval [CI] 0.5-1.7), 2.5 (95% CI 1.6-5.6), 8.7 (95% CI 5.2-18.9) and 27.2 (95% CI 11.8-50.3), respectively. No significant differences were found between the derivation and validation cohorts. Receiver operating characteristic (ROC) curves demonstrate a high predictive performance of the new index, with greater power to discriminate between the various classes of risk than the indexes currently used. The high predictive performance and simplicity of the UCRS make it suitable for wide-scale use in preoperative cardiac risk assessment of patients undergoing noncardiac surgery

The use of distance learning and e-learning in students with learning disabilities: A review on the effects and some hint of analysis on the use during covid-19 outbreak

Even if the use of distance learning and E-learning has a long tradition all over the world and both have been used to keep in contact with students and to provide lessons, support and learning materials, there is an open debate on the balance between advantages and disadvantages in the use of distance learning. This debate is even more central in their use to support students with Learning Disabilities (LDs), an overarching group of neurodevelopmental disorders that affect more than 5% of students. The current COVID-19 outbreak caused school closures and the massive use of E-learning all over the world and it put higher attention on the debate of the effects of E-learning. This paper aims to review papers that investigated the positive and negative effects of the use of Distance Learning and E-learning in students with LDs. We conducted a literature review on the relationship between Distance Learning, E-learning and Learning Disabilities, via Scopus, Eric and Google Scholar electronic database, according to Prisma Guidelines. The findings are summarized using a narrative, but systematic, approach. According to the data resulting from the papers, we also discuss issues to be analyzed in future research and in the use of E-learning during the current pandemic of COVID-19

Three-dimensional hydrostratigraphical modelling supporting the evaluation of fluoride enrichment in groundwater: Lakes basin (Central Ethiopia)

Study region: The Lakes Basin is located in the Main Ethiopian Rift. It covers the northern part of the rift valley basin, the Upper Awash River basin, and some sub-basins from the Omo River basin. Due to the presence of high fluoride (F−) content, natural contamination of groundwater has long been recognized as a water-related health issue in the area. Study focus: A multidisciplinary research effort, including geological, hydrogeological, hydro-chemical, and geophysical investigations, was adopted to understand the 3D hydrogeological conceptual model and to evaluate F− enrichment in groundwater. New hydrological insights for the region: The 3D hydrogeological conceptual model shows a complex hydrogeological environment and a clear hydraulic interconnection between different aquifers. The geological setting has deeply influenced the geometry of the aquifers, recharge and discharge areas, and F− enrichment in groundwater. Two hydrogeological units, namely sedimentary and volcanic multi-aquifers, were identified. The analyses of groundwater circulation, flow paths, and distribution of F- concentrations in each aquifer were conducted. In groundwater, the concentration of fluoride varies from 0.1 to 68.9 mg L−1; in surface water, it ranges from 0.6 to 244.2 mg L−1. Fluoride concentration of 62 % of the water samples analyzed exceeded the 1.5 mg L−1 WHO threshold for fluoride concentration in drinking water. The proposed methodological approach has been demonstrated to be a powerful tool that could be applied in other similar areas

The Exposure to Osteoarthritic Synovial Fluid Enhances the Immunomodulatory Profile of Adipose Mesenchymal Stem Cell Secretome

Objective. Several clinical studies have proposed the infusion of adipose mesenchymal stem cells (AMSCs) as an alternative therapy for joint diseases with inflammatory components, such as osteoarthritis. Indeed, AMSCs are able to stimulate tissue repair through a paracrine activity and the interaction with the inflammatory microenvironment seems to have a critical role. Design. To reproduce the inflammatory microenvironment, AMSCs were exposed to osteoarthritic synovial fluid (SF) for 48 h and the effect of their secretome on differentiation of monocytes (M0) into macrophages M1-like and mature dendritic cells (mDCs) was evaluated. Furthermore, the effect of the secretome of AMSCs exposed to SF was evaluated on the T cell population in terms of T cell proliferation and expansion of T regulatory cells (T reg). Results. Our data show that the exposure of AMSCs to SF activates cells and promotes the release of immunosuppressive factors, which induce macrophage polarization of M0 into the M2-like phenotype and inhibit differentiation of monocytes into mature dendritic cells (mDCs). Only the secretome of exposed AMSCs was able to inhibit T cell proliferation and promote T reg expansion. Conclusions. Our results suggest that the microenvironment plays a fundamental role for the development of anti-inflammatory and immunomodulatory properties of AMSCs

Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes

The predominant mechanism by which adipose mesenchymal stem cells (AMSCs) participate to tissue repair is through a paracrine activity and their communication with the inflammatory microenvironment is essential part of this process. This hypothesis has been strengthened by the recent discovery that stem cells release not only soluble factors but also extracellular vesicles, which elicit similar biological activity to the stem cells themselves. We demonstrated that the treatment with inflammatory cytokines increases the immunosuppressive and anti-inflammatory potential of AMSCs-derived exosomes, which acquire the ability to shift macrophages from M1 to M2 phenotype by shuttling miRNA regulating macrophages polarization. This suggests that the immunomodulatory properties of AMSCs-derived exosomes may be not constitutive, but are instead induced by the inflammatory microenvironment

Characterization of the Proinflammatory Profile of Synovial Fluid-Derived Exosomes of Patients with Osteoarthritis

The purpose of this study is to characterize synovial fluid- (SF-) derived exosomes of patients with gonarthrosis comparing two methods of isolation and to investigate their immune regulatory properties. Extracellular vesicles (EVs) have been isolated from inflamed SF by polymer precipitation method and quantified by Exocet kit and by nanoparticle tracking analysis. Vesicles expressed all the specific exosomal markers by immunoblot and FACS. After isolation with Exoquick, a relevant contamination by immune complexes was detected, which required further magnetic bead-based purification to remove. SF-derived exosomes significantly stimulated the release of several inflammatory cytokines and chemokines and metalloproteinases by M1 macrophages but did not influence the expression of CD80 and CD86 costimulatory molecules. In conclusion, we characterized purified exosomes isolated from inflamed SF and demonstrate that purified exosomes are functionally active in their ability to stimulate the release of proinflammatory factors from M1 macrophages. Our data indicate that SF-derived exosomes from gonarthrosis patients play a role in disease progression

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse