Tuning the reduction of graphene oxide nanoflakes differently affects neuronal networks in the zebrafish

The increasing engineering of biomedical devices and the design of drug-delivery platforms enriched by graphene-based components demand careful investigations of the impact of graphene-related materials (GRMs) on the nervous system. In addition, the enhanced diffusion of GRM-based products and technologies that might favor the dispersion in the environment of GRMs nanoparticles urgently requires the potential neurotoxicity of these compounds to be addressed. One of the challenges in providing definite evidence supporting the harmful or safe use of GRMs is addressing the variety of this family of materials, with GRMs differing for size and chemistry. Such a diversity impairs reaching a unique and predictive picture of the effects of GRMs on the nervous system. Here, by exploiting the thermal reduction of graphene oxide nanoflakes (GO) to generate materials with different oxygen/carbon ratios, we used a high-throughput analysis of early-stage zebrafish locomotor behavior to investigate if modifications of a specific GRM chemical property influenced how these nanomaterials affect vertebrate sensory-motor neurophysiology—exposing zebrafish to GO downregulated their swimming performance. Conversely, reduced GO (rGO) treatments boosted locomotor activity. We concluded that the tuning of single GRM chemical properties is sufficient to produce differential effects on nervous system physiology, likely interfering with different signaling pathways

Comparison of the diagnostic performance of 64-slice computed tomography coronary angiography in diabetic and non-diabetic patients with suspected coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Diabetics have high prevalence of subclinical coronary artery disease (CAD) with typical characteristics (diffuse disease, large calcifications). Although 64-slice multidetector computed tomography (MDCT) coronary angiography has high diagnostic accuracy to detect CAD, its diagnostic performance in diabetics with suspected CAD is unknown. To compare the diagnostic performance of 64-slice MDCT between diabetics and non-diabetics with suspected CAD scheduled for invasive coronary angiography (ICA).</p> <p>Methods</p> <p>We enrolled one hundred and five diabetic patients (92 men, age 65 +/- 9 years, Group 1) and 105 non-diabetic patients (63 men, age 63+/-5 years, Group 2) with indication to ICA for suspected CAD undergoing coronary 64-slice MDCT before ICA.</p> <p>Results</p> <p>In Group 1, the overall feasibility of coronary artery visualization was 93.8%. The most frequent artifact was blooming due to large coronary calcifications (54 artifacts, 67%). In Group 2, the overall feasibility was significantly higher vs. Group 1 (97%, p < 0.0001). In Group 1, the segment-based analysis showed a MDCT sensibility, specificity, positive predictive value, negative predictive value and accuracy for the detection of ≥50% luminal narrowing of 77%, 90%, 70%, 93% and 87%, respectively. In Group 2, all these parameters were significantly higher vs. Group 1. In the patient-based analysis, specificity, negative predictive value and accuracy were significantly lower in Group 1 vs. Group 2.</p> <p>Conclusions</p> <p>Although MDCT has high sensitivity for early identification of significant CAD in diabetics, its diagnostic performance is significantly reduced in these patients as compared to non-diabetics with similar clinical characteristics.</p

High results and lower cost in four-bone arthrodesis with retrograde screws

Aim To describe the technique of the four-corner fusion with two retrograde crossed headless screws in cases of carpal collapse. Methods This technique is a consolidated procedure performed in cases of scaphoid non- union advanced collapse (SNAC) type II and III, scapholunate advanced collapse (SLAC) type II and III and in other cases of carpal collapse. Between 2017 and 2019 we treated six male patients (a mean age of 55.0 years) with radiocarpal osteoarthritis. Our technique involves the use of two retrograde crossed headless screws; the first screw was placed distally proximally from the uncinate to the lunate and the second screw from the pyramidal to the capitate, crossed at approximately 90 degrees. Clinical and radiographic two-year follow-up was performed. Before the treatment and during the follow-ups VAS, PRWE and DASH Quick score scales, measured wrist range of motion (WROM) were administered and evaluated. Results In all cases the X-ray consolidation of arthrodesis within five months was noticed; in 50% patients already under 3-month control. No observed signs of mobilization of screws and inflammatory or infectious processes were found. All patients were satisfied (reduction/disappearance of pain). All surgically treated patients resumed normal daily activities. These improvements were confirmed by the results of the evaluation scale and clinical examination. Conclusion This technique, in our opinion, represents a gold standard. Its low costs of the material used (especially comparing to other technique), a low prevalence of complications of materials and fusion in 100% of cases should be also considered

Shedding Plasma Membrane Vesicles Induced by Graphene Oxide Nanoflakes in Brain Cultured Astrocytes

Microvesicles (MVs) generated and released by astrocytes, the brain prevalent cells, crucially contribute to intercellular communication, representing key vectorized systems able to spread and actively transfer signaling molecules from astrocytes to neurons, ultimately modulating target cell functions. The increasing clinical relevance of these signaling systems requires a deeper understanding of MV features, currently limited by both their nanoscale dimensions and the low rate of their constituent release. Hence, to investigate the features of such glial signals, nanotechnology-based approaches and the applications of unconventional, cost-effective tools in generating MVs are needed. Here, small graphene oxide (s-GO) nanoflakes are used to boost MVs shedding from astrocytes in cultures and s-GO generated MVs are compared with those generated by a natural stimulant, namely ATP, by atomic force microscopy, light scattering, attenuated total reflection\u2013fourier transform infra-red and ultraviolet resonance Raman spectroscopy. We also report the ability of both types of MVs, upon acute and transient exposure of patch clamped cultured neurons, to modulate basal synaptic transmission, inducing a stable increase in synaptic activity accompanied by changes in neuronal plasma membrane elastic features

Binuclear Copper(I) Complexes for Near-Infrared Light-Emitting Electrochemical Cells

Two binuclear heteroleptic CuI complexes, namely Cu−NIR1 and Cu−NIR2, bearing rigid chelating diphosphines and π-conjugated 2,5-di(pyridin-2-yl)thiazolo[5,4-d]thiazole as the bis-bidentate ligand are presented. The proposed dinuclearization strategy yields a large bathochromic shift of the emission when compared to the mononuclear counterparts (M1–M2) and enables shifting luminescence into the near-infrared (NIR) region in both solution and solid state, showing emission maximum at ca. 750 and 712 nm, respectively. The radiative process is assigned to an excited state with triplet metal-to-ligand charge transfer (3MLCT) character as demonstrated by in-depth photophysical and computational investigation. Noteworthy, X-ray analysis of the binuclear complexes unravels two interligand π–π-stacking interactions yielding a doubly locked structure that disfavours flattening of the tetrahedral coordination around the CuI centre in the excited state and maintain enhanced NIR luminescence. No such interaction is present in M1–M2. These findings prompt the successful use of Cu−NIR1 and Cu−NIR2 in NIR light-emitting electrochemical cells (LECs), which display electroluminescence maximum up to 756 nm and peak external quantum efficiency (EQE) of 0.43 %. Their suitability for the fabrication of white-emitting LECs is also demonstrated. To the best of our knowledge, these are the first examples of NIR electroluminescent devices based on earth-abundant CuI emitters

Tuning the Reduction of Graphene Oxide Nanoflakes Differently Affects Neuronal Networks in the Zebrafish

The increasing engineering of biomedical devices and the design of drug-delivery platforms enriched by graphene-based components demand careful investigations of the impact of graphene-related materials (GRMs) on the nervous system. In addition, the enhanced diffusion of GRM-based products and technologies that might favor the dispersion in the environment of GRMs nanoparticles urgently requires the potential neurotoxicity of these compounds to be addressed. One of the challenges in providing definite evidence supporting the harmful or safe use of GRMs is addressing the variety of this family of materials, with GRMs differing for size and chemistry. Such a diversity impairs reaching a unique and predictive picture of the effects of GRMs on the nervous system. Here, by exploiting the thermal reduction of graphene oxide nanoflakes (GO) to generate materials with different oxygen/carbon ratios, we used a high-throughput analysis of early-stage zebrafish locomotor behavior to investigate if modifications of a specific GRM chemical property influenced how these nanomaterials affect vertebrate sensory-motor neurophysiology—exposing zebrafish to GO downregulated their swimming performance. Conversely, reduced GO (rGO) treatments boosted locomotor activity. We concluded that the tuning of single GRM chemical properties is sufficient to produce differential effects on nervous system physiology, likely interfering with different signaling pathways

Essential but differential role for CXCR4 and CXCR7 in the therapeutic homingof human renal progenitor cells

Recently, we have identified a population of renal progenitor cells in human kidneys showing regenerative potential for injured renal tissue of SCID mice. We demonstrate here that among all known chemokine receptors, human renal progenitor cells exhibit high expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7. In SCID mice with acute renal failure (ARF), SDF-1 was strongly up-regulated in resident cells surrounding necrotic areas. In the same mice, intravenously injected renal stem/progenitor cells engrafted into injured renal tissue decreased the severity of ARF and prevented renal fibrosis. These beneficial effects were abolished by blocking either CXCR4 or CXCR7, which dramatically reduced the number of engrafting renal progenitor cells. However, although SDF-1–induced migration of renal progenitor cells was only abolished by an anti-CXCR4 antibody, transendothelial migration required the activity of both CXCR4 and CXCR7, with CXCR7 being essential for renal progenitor cell adhesion to endothelial cells. Moreover, CXCR7 but not CXCR4 was responsible for the SDF-1–induced renal progenitor cell survival. Collectively, these findings suggest that CXCR4 and CXCR7 play an essential, but differential, role in the therapeutic homing of human renal progenitor cells in ARF, with important implications for the development of stem cell–based therapies

Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment

Graphene and its derivatives are heralded as 'miracle' materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biological effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile