Obesity is causally linked with the development of cardiovascular disorders. Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesity-driven adipose tissue ...dysfunction that promotes a chronic inflammatory state within the organism. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. The microenvironment of adipose tissue will affect the adipokine secretome, having actions on remote tissues. Obesity typically leads to the upregulation of proinflammatory adipokines and the downregulation of anti-inflammatory adipokines, thereby contributing to the pathogenesis of cardiovascular diseases. In this review, we focus on the microenvironment of adipose tissue and how it influences cardiovascular disorders, including atherosclerosis and ischemic heart diseases, through the systemic actions of adipokines.
The ability of cells to follow gradients of extracellular matrix stiffness—durotaxis—has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited ...durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.
Lipases are the most widely used enzymes in biocatalysis, and the most utilized method for enzyme immobilization is using hydrophobic supports at low ionic strength. This method allows the one step ...immobilization, purification, stabilization, and hyperactivation of lipases, and that is the main cause of their popularity. This review focuses on these lipase immobilization supports. First, the advantages of these supports for lipase immobilization will be presented and the likeliest immobilization mechanism (interfacial activation on the support surface) will be revised. Then, its main shortcoming will be discussed: enzyme desorption under certain conditions (such as high temperature, presence of cosolvents or detergent molecules). Methods to overcome this problem include physical or chemical crosslinking of the immobilized enzyme molecules or using heterofunctional supports. Thus, supports containing hydrophobic acyl chain plus epoxy, glutaraldehyde, ionic, vinylsulfone or glyoxyl groups have been designed. This prevents enzyme desorption and improved enzyme stability, but it may have some limitations, that will be discussed and some additional solutions will be proposed (e.g., chemical amination of the enzyme to have a full covalent enzyme-support reaction). These immobilized lipases may be subject to unfolding and refolding strategies to reactivate inactivated enzymes. Finally, these biocatalysts have been used in new strategies for enzyme coimmobilization, where the most stable enzyme could be reutilized after desorption of the least stable one after its inactivation.
•Lipases immobilization on hydrophobic supports via interfacial activation is described in this review•This protocol permits the one step immobilization, purification, stabilization and hyperactivation of lipases•Lipases may be released from the support under certain conditions•Intermolecular crosslinking may prevent enzyme release•Heterofunctional supports prevent enzyme release but they have some limitations•There are many ways of taking full advantage of the new heterofunctional supports
Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently ...accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.
The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physicalchemical and biological characteristics. They are synthesized by the liver from ...cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species. Although their best- known role is their participation in the digestion and absorption of fat, they also play an important role in several other physiological processes. Thus, genetic abnormalities accounting for alterations in their synthesis, biotransformation and/or transport may result in severe alterations, even leading to lethal situations for which the sole therapeutic option may be liver transplantation. Moreover, the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis, resulting in damage to the liver parenchyma and, eventually, extrahepatic tissues. When this occurs during pregnancy, the outcome of gestation may be challenged. In contrast, the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.
Species distribution models (SDMs) are used to inform a range of ecological, biogeographical and conservation applications. However, users often underestimate the strong links between data type, ...model output and suitability for end-use. We synthesize current knowledge and provide a simple framework that summarizes how interactions between data type and the sampling process (i.e. imperfect detection and sampling bias) determine the quantity that is estimated by a SDM. We then draw upon the published literature and simulations to illustrate and evaluate the information needs of the most common ecological, biogeographical and conservation applications of SDM outputs. We find that, while predictions of models fitted to the most commonly available observational data (presence records) suffice for some applications, others require estimates of occurrence probabilities, which are unattainable without reliable absence records. Our literature review and simulations reveal that, while converting continuous SDM outputs into categories of assumed presence or absence is common practice, it is seldom clearly justified by the application's objective and it usually degrades inference. Matching SDMs to the needs of particular applications is critical to avoid poor scientific inference and management outcomes. This paper aims to help modellers and users assess whether their intended SDM outputs are indeed fit for purpose.
AIM: Species often remain undetected at sites where they are present. However, the impact of imperfect detection on species distribution models (SDMs) is not fully appreciated. In this paper we ...evaluate the influence of imperfect detection on the calibration and discrimination capacity of SDMs. We compare the performance of three types of SDMs: (1) a technique based on presence–absence data, (2) a technique based on presence–background data, and (3) a technique based on detection/non‐detection data that accounts for imperfect detection. INNOVATION: We use simulations to evaluate the impacts of imperfect detection in SDMs. This allows us to assess model performance with respect to the true objective of the models: the estimation of species distributions. We study a range of scenarios of occupancy and detection based on ecologically plausible environmental relationships and identify the circumstances in which imperfect detection affects model calibration and discrimination. We show that imperfect detection can substantially reduce the inferential and predictive accuracy of presence–absence and presence–background methods that do not account for detectability. While calibration is always affected, the influence on discrimination depends on the relationship of detectability and environmental variables. MAIN CONCLUSIONS: The performance of a model should be assessed with respect to its objectives. Comparative studies that intend to assess the performance of an SDM by evaluating its ability to predict detections rather than presences fail to reveal the benefits of accounting for detectability. Disregarding imperfect detection can have severe consequences for SDM performance, and hence for the estimation of species distributions. To date, this issue has been largely ignored in the SDM literature. Simultaneously modelling occupancy and detection does not necessarily require a greater sampling effort, but rather that data are collected so that they are informative about detectability. We recommend that consideration of imperfect detection become standard practice for species distribution modelling.
Background:
Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the ...most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations.
Methods:
Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council.
Results:
This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included.
Summary:
The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.
In this paper, we propose a sentiment-based approach to investigate the temporal and spatiotemporal effects on tourists' emotions when visiting a city's tourist destinations. Our approach consists of ...four steps: data collection and preprocessing from social media; visitor origin identification; visit sentiment identification; and temporal and spatiotemporal analysis. The temporal and spatiotemporal dimensions include day of the year, season of the year, day of the week, location sentiment progression, enjoyment measure, and multi-location sentiment progression. We apply this approach to the city of Chicago using over eight million tweets. Results show that seasonal weather, as well as special days and activities like concerts, impact tourists' emotions. In addition, our analysis suggests that tourists experience greater levels of enjoyment in places such as observatories rather than zoos. Finally, we find that local and international visitors tend to convey negative sentiment when visiting more than one attraction in a day whereas the opposite holds for out of state visitors.
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