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Neither acquiescence nor defiance: Tuscan wineries' "flexible reactivity" for the Italian national good quality legislations system.
Developmental neuronal remodeling shapes the mature connectivity of the nervous system in both vertebrates and invertebrates. Remodeling often combines degenerative and regenerative events, and defects in its normal progression have been linked to neurological disorders. Here we review recent progress that highlights the roles of cell-cell interactions during remodeling. We propose that these are fundamental to elucidating how spatiotemporal control of remodeling and coordinated circuit remodeling are achieved. We cover examples spanning various neuronal circuits in vertebrates and invertebrates and involving interactions between neurons and different cell types. PURPOSE To develop a phantom for methodological radiomic investigation on Magnetic Resonance (MR) images of female patients affected by pelvic cancer. METHODS A pelvis-shaped container was filled with a MnCl2 solution reproducing the relaxation times (T1, T2) of muscle surrounding pelvic malignancies. Inserts simulating multi-textured lesions were embedded in the phantom. The relaxation times of muscle and tumour were measured on an MR scanner on healthy volunteers and patients; T1 and T2 of MnCl2 solutions were evaluated with a relaxometer to find the concentrations providing a match to in vivo relaxation times. Radiomic features were extracted from the phantom inserts and the patients' lesions. Their repeatability was assessed by multiple measurements. RESULTS Muscle T1 and T2 were 1128 (806-1378) and 51 (40-65) ms, respectively. The phantom reproduced in vivo values within 13% (T1) and 12% (T2). T1 and T2 of tumour tissue were 1637 (1396-2121) and 94 (79-101) ms, respectively. learn more The phantom insert best mimicking the tumour agreed within 7% (T1) and 24% (T2) with in vivo values. Out of 1034 features, 75% (95%) had interclass correlation coefficient greater than 0.9 on T1 (T2)-weighted images, reducing to 33% (25%) if the phantom was repositioned. The most repeatable features on phantom showed values in agreement with the features extracted from patients' lesions. CONCLUSIONS We developed an MR phantom with inserts mimicking both relaxation times and texture of pelvic tumours. As exemplified with repeatability assessment, such phantom is useful to investigate features robustness and optimise the radiomic workflow on pelvic MR images. PURPOSE To present a formalism to improve the accuracy of converting absorbed dose to medium in medium (Dm) to absorbed dose to water in medium (Dw) in small megavoltage photon fields for different human tissues in Dm-based treatment planning systems (TPS). METHODS Eight kinds of real human tissues were simulated to convert Dm to Dw. Four kinds of virtual water media were deliberately designed to analyze source of deviations from the conventional Bragg-Gray theory. Mass electronic stopping powers were calculated using the ESTAR code. The phase-space data was generated by the EGSnrc/BEAMnrc Monte Carlo code. The dose deposition was calculated with the EGSnrc/DOSRZnrc code. Electron fluence spectra calculated with EGSnrc/FLURZnrc code were utilized to analyze fluence perturbations and determine fluence intensity (Φw,mint) and fluence spectral shape (Φw,mS) correction factors. RESULTS Large conversion errors of Dw using Bragg-Gray theory were observed, such as 19.65% ± 9.58% (average value ± standard deviation, type A) for inflated lung (ICRU). Fluence perturbations could be exacerbated by severe charged particle disequilibrium conditions. These deviations were caused by the synergy between tissues' different mean excitation energies and smaller mass densities compared to those of water. Adding Φw,mint and Φw,mS correction factors to modify Bragg-Gray theory could greatly reduce Dw conversion errors, within 1.00% for all tissues studied. CONCLUSIONS The current clinically used Dw conversion algorithm in commercial Dm-based TPS isn't appropriate for some human tissues in small field dosimetry. Correction factors should be exploited to improve the accuracy. Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial nephritis. However, whether omeprazole is toxic to renal cells is unknown. Omeprazole has a lethal effect over some cancer cells, and cell death is a key process in kidney disease. Thus, we evaluated the potential lethal effect of omeprazole over tubular cells. Omeprazole induced dose-dependent cell death in human and murine proximal tubular cell lines and in human primary proximal tubular cell cultures. Increased cell death was observed at the high concentrations used in cancer cell studies and also at lower concentrations similar to those in peptic ulcer patient serum. Cell death induced by omeprazole had features of necrosis such as annexin V/7-AAD staining, LDH release, vacuolization and irregular chromatin condensation. Weak activation of caspase-3 was observed but inhibitors of caspases (zVAD), necroptosis (Necrostatin-1) or ferroptosis (Ferrostatin-1) did not prevent omeprazole-induced death. However, omeprazole promoted a strong oxidative stress response affecting mitochondria and lysosomes and the antioxidant N-acetyl-cysteine reduced oxidative stress and cell death. By contrast, iron overload increased cell death. An adaptive increase in the antiapoptotic protein BclxL failed to protect cells. In mice, parenteral omeprazole increased tubular cell death and the expression of NGAL and HO-1, markers of renal injury and oxidative stress, respectively. In conclusion, omeprazole nephrotoxicity may be related to induction of oxidative stress and renal tubular cell death. Blunt abdominal trauma often presents a diagnostic challenge. Clinical examination demonstrates low reliability in detecting abdominal injury (16 %) when there is a history of head injury or loss of consciousness. This can prove detrimental, as delays in the diagnosis of traumatic bowel injury of 8 h or less can result in increased morbidity and mortality, as well as prolonged hospitalization. Although hemodynamically unstable patients will require an urgent laparotomy following clinical assessment, MDCT is the modality of choice for comprehensive imaging of blunt abdominal trauma in hemodynamically stable patients. Despite the use of MDCT, blunt injury to the bowel and mesentery, which accounts for up to 5% of injuries in cases of trauma, may be difficult to detect. The use of a constellation of direct and indirect signs on MDCT can help make the diagnosis and guide clinical management. Direct signs on MDCT, such as bowel wall discontinuity, and extraluminal gas may assist in the diagnosis of traumatic bowel injury.
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