Edge-Illumination X-Ray Dark-Field Tomography

Dark-field imaging is an x-ray technique used to highlight subpixel, typically micrometer-scale, density fluctuations. It is often used alongside standard attenuation-based and also phase-contrast x-ray imaging, which both see regular use in tomography. We present x-ray dark-field computed tomography (CT) with a laboratory edge-illumination setup. The dark-field contrast is shown to increase linearly with the x-ray path length through the imaged object, a prerequisite for the use of standard tomographic reconstruction approaches. A multimaterial, custom-built phantom is used to show how dark-field contrast CT can complement attenuation contrast CT for the separation of materials based on their microstructure. As an example of a more complex, biological sample, we present a model rat heart. We show, by comparison with attenuation contrast tomography, that dark-field enables the identification of additional structures undetected through the attenuation contrast channel, as well as offering a consistently sharper reconstructed image

Testing the performance of an innovative markerless technique for quantitative and qualitative gait analysis

Gait abnormalities such as high stride and step frequency/cadence (SF-stride/second, CAD-step/second), stride variability (SV) and low harmony may increase the risk of injuries and be a sentinel of medical conditions. This research aims to present a new markerless video-based technology for quantitative and qualitative gait analysis. 86 healthy individuals (mead age 32 years) performed a 90 s test on treadmill at self-selected walking speed. We measured SF and CAD by a photoelectric sensors system; then, we calculated average \ub1 standard deviation (SD) and within-subject coefficient of variation (CV) of SF as an index of SV. We also recorded a 60 fps video of the patient. With a custom-designed web-based video analysis software, we performed a spectral analysis of the brightness over time for each pixel of the image, that reinstituted the frequency contents of the videos. The two main frequency contents (F1 and F2) from this analysis should reflect the forcing/dominant variables, i.e., SF and CAD. Then, a harmony index (HI) was calculated, that should reflect the proportion of the pixels of the image that move consistently with F1 or its supraharmonics. The higher the HI value, the less variable the gait. The correspondence SF-F1 and CAD-F2 was evaluated with both paired t-Test and correlation and the relationship between SV and HI with correlation. SF and CAD were not significantly different from and highly correlated with F1 (0.893 \ub1 0.080 Hz vs. 0.895 \ub1 0.084 Hz, p < 0.001, r2 = 0.99) and F2 (1.787 \ub1 0.163 Hz vs. 1.791 \ub1 0.165 Hz, p < 0.001, r2 = 0.97). The SV was 1.84% \ub1 0.66% and it was significantly and moderately correlated with HI (0.082 \ub1 0.028, p < 0.001, r2 = 0.13). The innovative video-based technique of global, markerless gait analysis proposed in our study accurately identifies the main frequency contents and the variability of gait in healthy individuals, thus providing a time-efficient, low-cost means to quantitatively and qualitatively study human locomotion

[Glucocorticoid induced TNFR-related protein (GITR) as marker of human regulatory T cells: expansion of the GITR(+)CD25⁻ cell subset in patients with systemic lupus erythematosus].

Objectives: Regulatory T cells (TREG) represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/ inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR) is a well known marker of murine TREG cells, but little is known in humans. The aim of this study was to investigate the characteristics of TREG cells in systemic lupus erythematosus (SLE) and the potential role of GITR as marker of human TREG. Methods: Nineteen SLE patients and 15 sex- and age-matched normal controls (NC) were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR) using TaqMan probes. Results: The CD25highGITRhigh subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05). On the opposite, the CD25-GITRhigh cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01). Interestingly, FoxP3 at mRNA level was expressed in both CD25- GITRhigh and CD25highGITRhigh cells, suggesting that both cell subsets have regulatory activity. Conclusions: CD4+CD25-GITRhigh cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset

Volatile compared with total intravenous anaesthesia in patients undergoing high-risk cardiac surgery: a randomized multicentre study

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A DFT Study on the Efficacy of Linking Agents (Sulfur and Nitrogen) to Connect Trans-azobenzene Sandwiched Between Two Gold Electrodes

Electronic structure calculations were performed to analyze the effectiveness of linking agents (sulfur and nitrogen) in connecting the trans-azobenzene sandwiched between two gold surfaces (Au-atoms). It was analyzed the dynamics of the load carrier and the electronic structure of the molecular backbone by applying an external electric field (EF), also a detailed structural, frontier orbital and natural bond orbital analysis (NBO) were performed. From the NBO analysis, it was possible to predict the path of charge flow in the molecular system. Electrostatic potential mapping allowed us to visualize the charge redistribution in the molecular system caused by the EF application. Our results indicate that when the nitrogen atom is used as a linking agent, the azo group of molecules may enhance their conductivity. This work is licensed under a Creative Commons Attribution 4.0 International License

The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis

Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells (ESCs) with a differentiation-resistant, “hyper-pluripotent” state, which readily reprograms to a naive state resembling the preimplantation embryo. We further demonstrate that DDX6 plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner. Mechanistically, DDX6 mediates the translational suppression of target mRNAs in P-bodies. Upon loss of DDX6 activity, P-bodies dissolve and release mRNAs encoding fate-instructive transcription and chromatin factors that re-enter the ribosome pool. Increased translation of these targets impacts cell fate by rewiring the enhancer, heterochromatin, and DNA methylation landscapes of undifferentiated cell types. Collectively, our data establish a link between P-body homeostasis, chromatin organization, and stem cell potency

Decellularized skeletal muscles display neurotrophic effects in three‐dimensional organotypic cultures

Skeletal muscle decellularization allows the generation of natural scaffolds that retain the extracellular matrix (ECM) mechanical integrity, biological activity, and three‐dimensional (3D) architecture of the native tissue. Recent reports showed that in vivo implantation of decellularized muscles supports muscle regeneration in volumetric muscle loss models, including nervous system and neuromuscular junctional homing. Since the nervous system plays pivotal roles during skeletal muscle regeneration and in tissue homeostasis, support of reinnervation is a crucial aspect to be considered. However, the effect of decellularized muscles on reinnervation and on neuronal axon growth has been poorly investigated. Here, we characterized residual protein composition of decellularized muscles by mass spectrometry and we show that scaffolds preserve structural proteins of the ECM of both skeletal muscle and peripheral nervous system. To investigate whether decellularized scaffolds could per se attract neural axons, organotypic sections of spinal cord were cultured three dimensionally in vitro, in presence or in absence of decellularized muscles. We found that neural axons extended from the spinal cord are attracted by the decellularized muscles and penetrate inside the scaffolds upon 3D coculture. These results demonstrate that decellularized scaffolds possess intrinsic neurotrophic properties, supporting their potential use for the treatment of clinical cases where extensive functional regeneration of the muscle is required

Reply to the Letter to the Editor: The Italian Society of Rheumatology clinical practice guidelines for the management of polymyalgia rheumatica

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Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11¿966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57¿years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n¿=¿197), followed by diffuse large B-cell lymphoma (DLBCL) (n¿=¿67), nodal MZL lymphoma (n¿=¿29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n¿=¿19) and follicular lymphoma (FL) (n¿=¿17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8¿years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.Peer ReviewedPostprint (published version

Anti-beta 2 glycoprotein I antibodies in centenarians

Non-organ-specific autoantibodies are present in centenarians without evidence of autoimmune diseases but conflicting or no data on anti-phospholipid and anti-phospholipid binding proteins were reported. To investigate the presence and antigen specificity of anti-phospholipid and anti-phospholipid binding proteins in centenarians. Seventy-seven centenarians, 70 adult controls, 65 unselected elderly subjects, and 38 old SENIEUR volunteers were investigated. Anti-cardiolipin, anti-human \u3b22glycoprotein I, and lupus anticoagulant were detected. Antigen specificity was assayed against plates coated with anionic, neutral and cationic phospholipids and \u3b22glycoprotein I-dependence was also evaluated. 54.3% of the centenarians were positive for IgG and 8.6% for IgM anti-\u3b22glycoprotein I antibodies, while only 20.7% centenarians were positive for anti-cardiolipin IgG and 2.59% for IgM; none resulted positive for lupus anticoagulant. Anti-cardiolipin positive sera cross-reacted with negatively charged phospholipids and displayed decreased binding to serum-free cardiolipin-coated plates that was restored by human \u3b22glycoprotein I or fetal calf serum. Centenarians display high reactivity against human \u3b22glycoprotein I but low binding to the bovine molecule in the anti-cardiolipin assay. In spite of the presence of antibodies comparable to those found in patients with the anti-phospholipid syndrome, no vascular events were reported suggesting the presence of unknown protective factors and/or the lack of triggering factors