Background. Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone ...metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls. Aim. To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (n=20). Results. Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P=0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels (r=‐0.294, P=0.047) and urine calcium excretions (r=‐0.300, P=0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck (r=0.364, P=0.021) and total hip (r=0.353, P=0.015) T-scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women. Conclusions. In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.
Abstract Background and aims In coronary artery disease (CAD) epicardial adipose tissue (EAT) shows an elevated inflammatory infiltrate. Toll-like receptors (TLRs) are important mediators of adipose ...tissue inflammation and they are able to recognize endogenous products released by damaged cells. Because adipocyte death may be driven by hypertrophy, our aim was to investigate in CAD and non-CAD patients the association between EAT adipocyte size, macrophage infiltration/polarization and TLR-2 and TLR-4 expression. Methods and results EAT biopsies were collected from CAD and non-CAD patients. The adipocyte size was determined by morphometric analysis. Microarray technology was used for gene expression analysis; macrophage phenotype and TLRs expression were analyzed by immunofluorescence and immunohistochemical techniques. Inflammatory mediator levels were determined by immunoassays. EAT adipocytes were larger in CAD than non-CAD patients and do not express perilipin A, a marker of lipid droplet integrity. In CAD, EAT is more infiltrated by CD68-positive cells which are polarized toward an M1 state (CD11c positive) and presents an increased pro-inflammatory profile. Both TLR-2 and TLR-4 expression is higher in EAT from CAD and observed on all the CD68-positive cells. Conclusions Our findings suggested that EAT hypertrophy in CAD promotes adipocyte degeneration and drives local inflammation through increased infiltration of macrophages which are mainly polarized towards an M1 state and express both TLR-2 and TLR-4.
HfO 2 -based resistive RAMs have been irradiated with high-linear energy transfer heavy ions and subjected to an extensive characterization, showing that the cells are immune from upsets. No relevant ...changes were observed in the irradiated cells on resistance distribution and programming voltages. The irradiation experiment has been performed without any applied bias (retention mode). Reasons for the observed hardness are discussed using physics-based simulations. Moreover, simulations put in evidence that the cell might be sensitive if it is struck during a read operation, since the applied read voltage prevents the instantaneous recombination of the generated defects due to the Coulomb interaction between oxygen ions and vacancies.
Acute aortic dissection (AAD) is an event which may be rapidly fatal without early diagnosis and treatment. Aging is one of the main risk factors that could leading to AAD. To date, no specific ...biomarkers are available to increase the speed of diagnosis. CD40 ligand (CD40L), myeloperoxidase (MPO), matrix metalloproteinase (MMP)-1, -2, -9 and metallopeptidase tissue inhibitor 1 (TIMP-1) are biologically related molecules which integrate inflammation, tissue injury and remodeling, all events associated to AAD. Our is a pilot study to evaluate whether circulating levels of these molecules may be used as potential biomarkers in timely diagnosis of AAD.
Within 24 h of symptom onset, circulating CD40L, MPO, MMP-1,-2,-9 and TIMP-1 were quantified by enzyme-linked immunosorbent assays in 22 patients (40-86 years of age) with AAD of ascending aorta (type A according to Stanford classification) and 11 patients with AAD of descending aorta (type B). 30 healthy individuals age matched were used as control group compared to controls, both type A and B AAD patients had higher CD40L (p < 0.001) and MPO (p < 0.01) levels. MMP-1 was higher in the overall AAD group (p < 0.01). After Stanford classification, type A group had increased level compared to both control and type B (p < 0.01 and p < 0.05, respectively). TIMP-1 was higher in both A and B groups compared to controls (p < 0.001). No differences were observed in MMP-2 and MMP-9 levels.
The simultaneous evaluation of CD40L, MPO and MMP-1 and TIMP-1, which may contribute to structural changes in aortic tissue in AAD patients, seems to be a novel promising diagnostic panel.
Energy efficiency remains a challenge for the design of non-volatile resistive memories (ReRAMs) arrays. This memory technology suffers from intrinsic variability in switching speed, programming ...voltages, and resistance levels. The programming conditions of memory elements (e.g., pulse widths and amplitudes) must cover the tail bits to avoid programming failures. Switching time of ReRAMs shows wide distributions. Therefore, fast cells are subjects for electrical stress after their switching and energy waste since programming currents are typically large for this technology (tens of μA). In this brief, we present a write termination (WT) circuit to stop the programming operation when the switching event occurs in the selected memory element. The proposed design is sensitive to current variations that take place when the memory element switches between two different resistance states (low resistance state and high resistance state). This WT scheme reduces the power consumption by 97+%, 93+%, and 65+% during Forming, RESET and SET operations respectively. Our estimations show that area efficiency of 70% for a memory array is achievable when the presented WT circuit is integrated in near-memory peripheries. The demonstrated WT circuit is suitable for different ReRAM technologies with small overhead penalty and shows robustness against CMOS and ReRAM variabilities.
Abstract Background and aims Alterations in epicardial adipose tissue (EAT) biology ( i.e. increased fat thickness and inflammation) have been described in coronary artery disease (CAD) patients. In ...addition to its classic role in the regulation of calcium-phosphate homeostasis, vitamin D may exert immune-regulatory and anti-inflammatory effects. Whether EAT inflammation may be linked to vitamin D deficiency is still unknown. In the present study we evaluated plasma 25-hydroxycholecalciferol (25OHD) level in CAD patients and its relationship with EAT ability to locally metabolize vitamin D, EAT expression of inflammation-related molecules and EAT thickness. Methods and results Plasma 25OHD level was quantified by an immunoluminometric assay. EAT expression of inflammation-related molecules (MCP-1, PTX3, TNFα, IL-6, adiponectin), vitamin D receptor (VDR), CYP27B1 (25OHD-activating enzyme) and CYP24A1 (1,25-dihydroxycholecalciferol-metabolizing enzyme) was performed by microarray. EAT thickness was quantified by echocardiography. Median plasma 25OHD level was 10.85 ng/mL and 83% of CAD patients displayed 25OHD level below 20 ng/mL. At decreasing plasma 25OHD concentration, we observed a down-regulation in CYP27B1 and CYP24A1 level and an increased expression of VDR and pro-inflammatory cytokines (MCP-1, PTX3, TNFα, IL-6) at EAT level. No correlation was observed between plasma 25OHD level and EAT thickness. Conclusion Our data suggest an increased activation of inflammatory pathways at EAT level possibly related to systemic and local vitamin D deficiency in CAD patients. Whether maintaining an optimal vitamin D status may be helpful to reduce EAT inflammation and to prevent CAD and its progression needs further investigation.
Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells ...(TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs’ proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.
Contemporary distributed computing infrastructures (DCIs) are not easily and securely accessible by scientists. These computing environments are typically hard to integrate due to interoperability ...problems resulting from the use of different authentication mechanisms, identity negotiation protocols and access control policies. Such limitations have a big impact on the user experience making it hard for user communities to port and run their scientific applications on resources aggregated from multiple providers. The INDIGO-DataCloud project wants to provide the services and tools needed to enable a secure composition of resources from multiple providers in support of scientific applications. In order to do so, a common AAI architecture has to be defined that supports multiple authentication mechanisms, support delegated authorization across services and can be easily integrated in off-the-shelf software. In this contribution we introduce the INDIGO Authentication and Authorization Infrastructure, describing its main components and their status and how authentication, delegation and authorization flows are implemented across services.
Spiking Neural Networks (SNNs) can unleash the full power of analog Resistive Random Access Memories (RRAMs) based circuits for low power signal processing. Their inherent computational sparsity ...naturally results in energy efficiency benefits. The main challenge implementing robust SNNs is the intrinsic variability (heterogeneity) of both analog CMOS circuits and RRAM technology. In this work, we assessed the performance and variability of RRAM-based neuromorphic circuits that were designed and fabricated using a 130 nm technology node. Based on these results, we propose a Neuromorphic Hardware Calibrated (NHC) SNN, where the learning circuits are calibrated on the measured data. We show that by taking into account the measured heterogeneity characteristics in the off-chip learning phase, the NHC SNN self-corrects its hardware non-idealities and learns to solve benchmark tasks with high accuracy. This work demonstrates how to cope with the heterogeneity of neurons and synapses for increasing classification accuracy in temporal tasks.
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