Ultrasound Guidance in Paravertebral Injections of Oxygen-Ozone: Treatment of Low Back Pain

Background: Paravertebral injection of ozone is an established clinical practice for the treatment of Low Back Pain (LBP). The role of Ultrasound Guidance (USG) in mini invasive procedures has become important in many clinical practice thanks to the greater precision this technique can add. As matter of fact, a large volume of ozone in a single administration may have some adverse or side effects. In this study we wanted to verify if the use of USG in Oxygen/ Ozone (O2/O3) infiltrations could allow the administration of a smaller volume of gas mixture, increasing the safety and the comfort of the procedure itself, obtaining however similar or better results in pain decrease. Methods: We compared two groups of 25 patients affected by LBP, undergoing 10 infiltrations of O2/O3, by using USG (group U) or only anatomical landmarks (group AL). Pain intensity, by calculating Visual Analogical Scale (VAS) difference before and after the treatment, and the discomfort were evaluated in both groups. Results: The mean of the VAS before the treatment was 6.44 in group U and 6.48 in group AL. The mean of the VAS after the treatment was 2.22 in group U and 3.04 in group AL. The mean of discomfort rate was 2.84 in group U and 5.44 in group AL. The number of patients with unbearable discomfort was 0 in group U and 7 in group AL. Conclusions: As many other treatment, also paravertebral injections of O2/O3 benefits of the advantages of the US device which makes this treatment safer and more accurate

Unresolved sources naturally contribute to PeV γ\gamma-ray diffuse emission observed by Tibet ASγ\gamma

The Tibet AS$\gamma$ experiment provided the first measurement of the total diffuse gamma-ray emission from the Galactic disk in the sub-PeV energy range. Based on the analysis of TeV sources included in the HGPS catalog, we predict the expected contribution of unresolved sources in the two angular windows of the Galactic plane observed by Tibet AS$\gamma$. We show that the sum of this additional diffuse component due to unresolved sources and the truly diffuse emission, due to cosmic ray interaction with the interstellar medium, well saturates the Tibet data, without the need to introduce a progressive hardening of the cosmic-ray spectrum toward the Galactic center

Multiscale, patient-specific computational fluid dynamics models predict formation of neointimal hyperplasia in saphenous vein grafts

Stenosis due to neointimal hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers is insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics simulations of flow in the lumen and a biochemical model representing NIH growth mechanisms inside the vessel wall. For all three patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography scans

An in silico study of the influence of vessel wall deformation on neointimal hyperplasia progression in peripheral bypass grafts

Neointimal hyperplasia (NIH) is a major obstacle to graft patency in the peripheral arteries. A complex interaction of biomechanical factors contribute to NIH development and progression, and although haemodynamic markers such as wall shear stress have been linked to the disease, these have so far been insufficient to fully capture its behaviour. Using a computational model linking computational fluid dynamics (CFD) simulations of blood flow with a biochemical model representing NIH growth mechanisms, we analyse the effect of compliance mismatch, due to the presence of surgical stitches and/or to the change in distensibility between artery and vein graft, on the haemodynamics in the lumen and, subsequently, on NIH progression. The model enabled to simulate NIH at proximal and distal anastomoses of three patient-specific end-to-side saphenous vein grafts under two compliance-mismatch configurations, and a rigid wall case for comparison, obtaining values of stenosis similar to those observed in the computed tomography (CT) scans. The maximum difference in time-averaged wall shear stress between the rigid and compliant models was 3.4 Pa, and differences in estimation of NIH progression were only observed in one patient. The impact of compliance on the haemodynamic-driven development of NIH was small in the patient-specific cases considered

The Influence of Minor Aortic Branches in Patient-Specific Flow Simulations of Type-B Aortic Dissection.

Type-B aortic dissection (TBAD) is a disease in which a tear develops in the intimal layer of the descending aorta forming a true lumen and false lumen (FL). Because disease outcomes are thought to be influenced by haemodynamic quantities such as pressure and wall shear stress (WSS), their analysis via numerical simulations may provide valuable clinical insights. Major aortic branches are routinely included in simulations but minor branches are virtually always neglected, despite being implicated in TBAD progression and the development of complications. As minor branches are estimated to carry about 7-21% of cardiac output, neglecting them may affect simulation accuracy. We present the first simulation of TBAD with all pairs of intercostal, subcostal and lumbar arteries, using 4D-flow MRI (4DMR) to inform patient-specific boundary conditions. Compared to an equivalent case without minor branches, their inclusion improved agreement with 4DMR velocities, reduced time-averaged WSS (TAWSS) and transmural pressure and elevated oscillatory shear in regions where FL dilatation and calcification were observed in vivo. Minor branch inclusion resulted in differences of 60-75% in these metrics of potential clinical relevance, indicating a need to account for minor branch flow loss if simulation accuracy is sought

The Influence of Minor Aortic Branches in Patient-Specific Flow Simulations of Type-B Aortic Dissection

Type-B aortic dissection (TBAD) is a disease in which a tear develops in the intimal layer of the descending aorta forming a true lumen and false lumen (FL). Because disease outcomes are thought to be influenced by haemodynamic quantities such as pressure and wall shear stress (WSS), their analysis via numerical simulations may provide valuable clinical insights. Major aortic branches are routinely included in simulations but minor branches are virtually always neglected, despite being implicated in TBAD progression and the development of complications. As minor branches are estimated to carry about 7–21% of cardiac output, neglecting them may affect simulation accuracy. We present the first simulation of TBAD with all pairs of intercostal, subcostal and lumbar arteries, using 4D-flow MRI (4DMR) to inform patient-specific boundary conditions. Compared to an equivalent case without minor branches, their inclusion improved agreement with 4DMR velocities, reduced time-averaged WSS (TAWSS) and transmural pressure and elevated oscillatory shear in regions where FL dilatation and calcification were observed in vivo. Minor branch inclusion resulted in differences of 60-75% in these metrics of potential clinical relevance, indicating a need to account for minor branch flow loss if simulation accuracy is sought

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the con-tribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents

Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23

Guanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those that showed a high purinoreceptor similarity and were expressed in glioma cells, where GBPs exerted a powerful antiproliferative effect. Of the GPRs chosen, only the silencing of GPR23, also known as lysophosphatidic acid (LPA) 4 receptor, counteracted GBP-induced growth inhibition in U87 cells. Guanine (GUA) was the most potent compound behind the GPR23-mediated effect, acting as the endpoint effector of GBP antiproliferative effects. Accordingly, cells stably expressing GPR23 showed increased sensitivity to GUA. Furthermore, while GPR23 expression was low in a hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)-mutated melanoma cell line showing poor sensitivity to GBPs, and in HGPRT-silenced glioma cells, GPR23-induced expression in both cell types rescued GUA-mediated cell growth inhibition. Finally, binding experiments using [H-3]-GUA and U87 cell membranes revealed the existence of a selective GUA binding (K-D = 29.44 & PLUSMN; 4.07 nM; Bmax 1.007 & PLUSMN; 0.035 pmol/mg prot) likely to GPR23. Overall, these data suggest GPR23 involvement in modulating responses to GUA in tumor cell lines, although further research needs to verify whether this receptor mediates other GUA effects

Aneurysmal growth in type-B aortic dissection: assessing the impact of patient-specific inlet conditions on key haemodynamic indices

Type-B aortic dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, haemodynamic factors are believed to play a key role. Computational fluid dynamics (CFD) and 4D-flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (4D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 4D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations

Aneurysmal growth in type-B aortic dissection: assessing the impact of patient-specific inlet conditions on key haemodynamic indices

Type-B aortic dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, haemodynamic factors are believed to play a key role. Computational fluid dynamics (CFD) and 4D-flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (4D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 4D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations