Gene deficiency in activating Fcγ receptors influences the macrophage phenotypic balance and reduces atherosclerosis in mice

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fcγ receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in γ-chain (the common signaling subunit of activating Fcγ receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fcγ receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fcγ receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fcγ receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-κB activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fcγ receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fcγ receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fcγ receptor-mediated inflammatory responses could effectively suppress atherosclerosis

Serum levels and removal by haemodialysis and haemodiafiltration of tryptophan-derived uremic toxins in ESKD patients

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses

Yearly evolution of organ damage markers in diabetes or metabolic syndrome: data from the LOD-DIABETES study

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease morbidity-mortality is greater in people with type 2 diabetes mellitus or metabolic syndrome. The purpose of this study was to evaluate the yearly evolution of organ damage markers in diabetes or metabolic syndrome, and to analyze the associated factors.</p> <p>Methods</p> <p>An observational prospective study was carried out in the primary care setting, involving 112 patients: 68 diabetics and 44 subjects with metabolic syndrome, subjected to 12 months of follow-up. Measurements: traditional cardiovascular risk factors (blood pressure, blood glucose, lipids, smoking, body mass index (BMI) and) and non-traditional risk factors (waist circumference, hsC Reactive Protein and fibrinogen); subclinical vascular (carotid intima-media thickness, pulse wave velocity and ankle/brachial index), cardiac (Cornell voltage-duration product), renal organ damage (creatinine, glomerular filtration and albumin/creatinine index), and antihypertensive and lipid-lowering drugs.</p> <p>Results</p> <p>At baseline, the diabetics presented a mean age of 59.9 years, versus 55.2 years in the subjects with metabolic syndrome (p = 0.03). Diastolic blood pressure, total cholesterol and HDL-cholesterol were lower among the patients with diabetes, while blood glucose and HbA1c, as well as antihypertensive and lipid-lowering drug use, were greater. At evaluation after one year, the diabetics showed a decrease in BMI (-0.39), diastolic blood pressure (-3.59), and an increase in fibrinogen (30.23 mg/dL), ankle/brachial index (0.07) and the number of patients with ankle/brachial index pathologic decreased in 6. In turn, the patients with metabolic syndrome showed an increase in HDL-cholesterol (1-91 mg/dL), fibrinogen (25.54 mg/dL), Cornell voltage-duration product (184.22 mm/ms), ankle/brachial index (0.05) and the use of antihypertensive and lipid-lowering drugs, and a reduction in serum glucose (3.74 mg/dL), HOMA, systolic (-6.76 mmHg), diastolic blood pressure (-3.29 mmHg), and pulse wave velocity (-0.72 m/s). The variable that best predicted a decrease in pulse wave velocity in subjects with metabolic syndrome was seen to be an increase in antihypertensive drug use.</p> <p>Conclusions</p> <p>The annual assessment of cardiovascular risk factors and the decrease in pulse wave velocity was more favorable in the patients with metabolic syndrome, probably influenced by the increased percentage of subjects treated with antihypertensive and lipid lowering drugs in this group.</p

Wildlife surveillance using deep learning methods

Wildlife conservation and the management of human–wildlife conflicts require cost‐effective methods of monitoring wild animal behavior. Still and video camera surveillance can generate enormous quantities of data, which is laborious and expensive to screen for the species of interest. In the present study, we describe a state‐of‐the‐art, deep learning approach for automatically identifying and isolating species‐specific activity from still images and video data. We used a dataset consisting of 8,368 images of wild and domestic animals in farm buildings, and we developed an approach firstly to distinguish badgers from other species (binary classification) and secondly to distinguish each of six animal species (multiclassification). We focused on binary classification of badgers first because such a tool would be relevant to efforts to manage Mycobacterium bovis (the cause of bovine tuberculosis) transmission between badgers and cattle. We used two deep learning frameworks for automatic image recognition. They achieved high accuracies, in the order of 98.05% for binary classification and 90.32% for multiclassification. Based on the deep learning framework, a detection process was also developed for identifying animals of interest in video footage, which to our knowledge is the first application for this purpose. The algorithms developed here have wide applications in wildlife monitoring where large quantities of visual data require screening for certain species

The impact of a large object with Jupiter in July 2009

On 2009 July 19, we observed a single, large impact on Jupiter at a planetocentric latitude of 55^{\circ}S. This and the Shoemaker-Levy 9 (SL9) impacts on Jupiter in 1994 are the only planetary-scale impacts ever observed. The 2009 impact had an entry trajectory opposite and with a lower incidence angle than that of SL9. Comparison of the initial aerosol cloud debris properties, spanning 4,800 km east-west and 2,500 km north-south, with those produced by the SL9 fragments, and dynamical calculations of pre-impact orbit, indicate that the impactor was most probably an icy body with a size of 0.5-1 km. The collision rate of events of this magnitude may be five to ten times more frequent than previously thought. The search for unpredicted impacts, such as the current one, could be best performed in 890-nm and K (2.03-2.36 {\mu}m) filters in strong gaseous absorption, where the high-altitude aerosols are more reflective than Jupiter's primary cloud.Comment: 15 pages, 5 figure

Study of scintillation in natural and synthetic quartz and methacrylate

Samples from different materials typically used as optical windows or light guides in scintillation detectors were studied in a very low background environment, at the Canfranc Underground Laboratory, searching for scintillation. A positive result can be confirmed for natural quartz: two distinct scintillation components have been identified, not being excited by an external gamma source. Although similar effect has not been observed neither for synthetic quartz nor for methacrylate, a fast light emission excited by intense gamma flux is evidenced for all the samples in our measurements. These results could affect the use of these materials in low energy applications of scintillation detectors requiring low radioactive background conditions, as they entail a source of background.Comment: Accepted for publication in Optical Material

Dynamical Processing of Geophysical Signatures based on SPOT-5 Remote Sensing Imagery

An intelligent post-processing computational paradigm based on the use of dynamical filtering techniques modified to enhance the quality of reconstruction of geophysical signatures based on Spot-5 imagery is proposed. As a matter of particular study, a robust algorithm is reported for the analysis of the dynamic behavior of geophysical indexes extracted from the real-world remotely sensed scenes. The simulation results verify the efficiency of the approach as required for decision support in resources management