241 research outputs found

    Adipose tissue macrophages as potential targets for obesity and metabolic diseases

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    Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9+ macrophages, lipid-associated macrophages, DARC+ macrophages, and MFehi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases

    Future-proofing hydrogeology by revising groundwater monitoring practice

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    Groundwater is an important global resource and its sustainable use faces major challenges. New methods and advances in computational science could lead to much improved understanding of groundwater processes and subsurface properties. A closer look at current groundwater monitoring practice reveals the need for updates with a special focus on the benefits of high-frequency and high-resolution datasets. To future-proof hydrogeology, this paper raises awareness about the necessity for improvement, provides initial recommendations and advocates for the development of universal guide-lines

    Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

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    Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection

    Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

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    Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery

    Minimally Invasive Mitral Valve Surgery III: Training and Robotic-Assisted Approaches.

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    Minimally invasive mitral valve operations are increasingly common in the United States, but robotic-assisted approaches have not been widely adopted for a variety of reasons. This expert opinion reviews the state of the art and defines best practices, training, and techniques for developing a successful robotics program

    Future-proofing hydrogeology by revising groundwater monitoring practice

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    Groundwater is an important global resource and its sustainable use faces major challenges. New methods and advances in computational science could lead to much improved understanding of groundwater processes and subsurface properties. A closer look at current groundwater monitoring practice reveals the need for updates with a special focus on the benefits of high-frequency and high-resolution datasets. To future-proof hydrogeology, this technical note raises awareness about the necessity for improvement, provides initial recommendations and advocates for the development of universal guidelines

    HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation

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    During the past decade, catheter ablation of atrial fibrillation (AF) has evolved rapidly from a highly experimental unproven procedure, to its current status as a commonly performed ablation procedure in many major hospitals throughout the world. Surgical ablation of AF, using either standard or minimally invasive techniques, is also performed in many major hospitals throughout the world. The purpose of this Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF, and to report the findings of a Task Force, convened by the Heart Rhythm Society and charged with defining the indications, techniques, and outcomes of this procedure. The Heart Rhythm Society was pleased to develop this Consensus Statement in partnership with the European Heart Rhythm Association and the European Cardiac Arrhythmia Society. This statement summarizes the opinion of the Task Force members based on their own experience in treating patients, as well as a review of the literature, and is directed to all health care professionals who are involved in the care of patients with AF, particularly those who are undergoing or are being considered for catheter or surgical ablation procedures for AF. This statement is not intended to recommend or promote catheter ablation of AF. Rather the ultimate judgment regarding care of a particular patient must be made by the health care provider and patient in light of all the circumstances presented by that patient. In writing a "consensus" document, it is recognized that consensus does not mean that there was complete agreement among all Task Force members. We attempted to identify those aspects of AF ablation for which a true "consensus" could be identified ( Tables 1 and 2 ). Surveys of the entire Task Force were used to identify these areas of consensus. The main objective of this document is

    Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection

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    © 2015 Vilar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.BACKGROUND: Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD. DESIGN: Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined. RESULTS: Of the 341 patients studied, 64% had urine output>100 ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual = 160.3 · (1/β2m) - 4.2. Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2 ml/min/1.73 m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2 mg/L allowed identification of patients with urea clearance ≥2 ml/min/1.73 m2 with 90% specificity and 65% sensitivity. CONCLUSION: Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use of cut-off levels to identify patients with RKF may provide a simple way to individualise dialysis dose based on RKF.Peer reviewe

    Genetic Evidence for the Association between the Early Growth Response 3 (EGR3) Gene and Schizophrenia

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    Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3) gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb) in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3) showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016) and allele frequency distribution (P = 0.009). Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012); a significant difference was found for the common haplotype AG (P = 0.0005). Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001). In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis
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