Glass transition and cooperative rearranging regions in amorphous thermoplastic nanocomposites

The aim of this work was to study the effect of nanofillers on the structural relaxation phenomena occurring in amorphous poly(ethylene-terephthalate)/poly(cyclohexane-dimethanol terephthalate) copolymer (PET/PCHDMT) nanocomposites in correspondence with the glass transition temperature. PET/PCHDMT nanocomposites were prepared by melt mixing with an organicmodified montmorillonite at different processing temperatures. Differential scanning calorimetry analysis revealed that addition of the organic modifier alone causes a decrease of the glass transition temperature and an increase of the specific heat discontinuity. Nanocomposites showed a higher glass transition temperature and a lower specific heat discontinuity compared with samples obtained by adding organic modifier to PET/PCHDMT. Both effects were more relevant for samples processed at lower temperatures. Therefore, the glass transition temperature was studied by introducing the concept of fictive temperature and relaxation time. It was found that nanocomposites have a higher apparent activation energy and an increased size of cooperatively rearranging regions compared with neat PET/PCHDMT. Both effects are more relevant for nanocomposites processed at lower temperatures. All the discussed effects are explained by considering the enhanced confinement of PET/PCHDMT macromolecules, due to the presence of intercalated lamellae of organofiller. The efficiency of intercalation is increased by decreased processing temperature, which involves an increase of the nano-confinement area of the polymer

RAAS Inhibitor Prescription and Hyperkalemia Event in Patients With Chronic Kidney Disease: A Single-Center Retrospective Study

Hyperkalemia is common in patients treated with renin–angiotensin–aldosterone system inhibitors (RAASis), and it represents the main cause of the large gap reported between guideline recommendations and real-world practice in chronic kidney disease (CKD). We conducted a CKD-population-based restrospective study to determine the prevalence of patients with CKD treated with RAASis, incidence of hyperkalemia in patients with CKD treated with RAASis, and proportion of patients with RAASi medication change after experiencing incident hyperkalemia. Among 809 patients with CKD analyzed, 556 (68.7%) were treated with RAASis, and RAASi prescription was greater in stages 2–4 of CKD. Hyperkalemia occurred in 9.2% of RAASi-treated patients, and the adjusted rate of hyperkalemia among patients with stage 4–5 CKD was 3-fold higher compared with patients with eGFR > 60 ml/min/1.73 m(2). RAASi treatment was discontinued in 55.3% of the patients after hyperkalemia event (74.2% discontinued therapy, 3.2% received a reduced dose, and 22.6% reduced the number of RAASi drugs). This study shows that the incidence of hyperkalemia is frequently observed in patients with CKD patients with RAASis, and that rates increase with deteriorating levels of kidney function from stages 1 to 3. RAASi medication change following an episode of hyperkalemia occurred in almost half of the patients after experiencing hyperkalemia

FP534EXTRACORPOREAL TREATMENTS FOR LIGHT CHAIN REMOVAL IN MYELOMA-INDUCED CAST NEPHROPATHY

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Gastric cancer is the leading cause of death in Italian adult patients with common variable immunodeficiency

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7\u20133.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4\u201322.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2\u201312.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2\u201344.4 and HR: 4.2, 95%CI: 2.8\u201344.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines

Treatment and Long-Term Sequelae in Childhood Brain Tumors

In children treated for brain tumors, important deficits in cognitive development have been described. The reduction of Intelligence Quotient (IQ) is correlated with multiple conditions such as tumor location, obstructive hydrocephalus, surgical intervention, and above all, the use of radiotherapy, especially in young children. Demyelinization represents the most striking microscopic alteration following radiation: cerebral white matter's loss and failure to white matter development could partly account for changes in IQ score.Recently, combined chemo-radiotherapeutic approaches and the improvement of radiotherapy techniques have enabled the reduction of neurocognitive symptoms and improved the standard of life of childhood brain tumor survivors

The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials

Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22â1.02). No significant difference was shown in term of tSRE (HR 0.99, 95% CI 0.83â1.17). In conclusion, abiraterone and enzalutamide have both demonstrated to significantly delay the bone progression resulting in similar improvements in bone-related endpoints in patients with mCRPC

Physiological role of Prion Protein in Copper homeostasis and angiogenic mechanisms of endothelial cells

Abstract The Prion Protein (PrP) is mostly known for its role in prion diseases, where its misfolding and aggregation can cause fatal neurodegenerative conditions such as the bovine spongiform encephalopathy and human Creutzfeldt–Jakob disease. Physiologically, PrP is involved in several processes including adhesion, proliferation, differentiation and angiogenesis, but the molecular mechanisms behind its role remain unclear. PrP, due to its well-described structure, is known to be able to regulate copper homeostasis; however, copper dyshomeostasis can lead to developmental defects. We investigated PrP-dependent regulation of copper homeostasis in human endothelial cells (HUVEC) using an RNA-interference protocol. PrP knockdown did not influence cell viability in silenced HUVEC (PrPKD) compared to control cells, but significantly increased PrPKD HUVEC cells sensitivity to cytotoxic copper concentrations. A reduction of PrPKD cells reductase activity and copper ions transport capacity was observed. Furthermore, PrPKD-derived spheroids exhibited altered morphogenesis and their derived cells showed a decreased vitality 24 and 48 hours after seeding. PrPKD spheroid-derived cells also showed disrupted tubulogenesis in terms of decreased coverage area, tubule length and total nodes number on matrigel, preserving unaltered VEGF receptors expression levels. Our results highlight PrP physiological role in cellular copper homeostasis and in the angiogenesis of endothelial cells

The Immunohistochemical Loss of H3K27me3 in Intracranial Meningiomas Predicts Shorter Progression-Free Survival after Stereotactic Radiosurgery

The immunohistochemical loss of histone H3 trimethylated in lysine 27 (H3K27me3) was recently shown to predict recurrence of meningiomas after surgery. However, its association with tumor progression after stereotactic radiosurgery (SRS) is unexplored. To investigate whether H3K27 methylation status may predict progression-free survival (PFS) after SRS, we assessed H3K27me3 immunoexpression in thirty-nine treatment naïve, intracranial, meningiomas, treated with surgery and subsequent SRS for residual (twenty-three cases) or recurrent (sixteen cases) disease. H3K27me3 immunostaining was lost in seven meningiomas, retained in twenty-seven and inconclusive in five. Six of the seven meningiomas (86%) with H3K27me3 loss had tumor progression after SRS, compared to nine of twenty-seven (33%) with H3K27me3 retention (p = 0.0143). In addition, patients harboring a meningioma with H3K27me3 loss had significantly shorter PFS after SRS (range: 10-81 months; median: 34 months), compared to patients featuring a meningioma with retained H3K27me3 (range: 9-143 months; median: 62 months) (p = 0.0036). Nonetheless, tumor sagittal location was the only significant prognostic variable at multivariate analysis for PFS after SRS (p = 0.0142). These findings suggest a previously unreported role of H3K27me3 as a predictor of meningioma progression after SRS for recurrent or residual disease. Modulation of H3K27 methylation status may represent a novel therapeutic strategy to induce radiosensitization of meningiomas

Simplified Models for Dark Matter and Missing Energy Searches at the LHC

The study of collision events with missing energy as searches for the dark matter (DM) component of the Universe are an essential part of the extensive program looking for new physics at the LHC. Given the unknown nature of DM, the interpretation of such searches should be made broad and inclusive. This report reviews the usage of simplified models in the interpretation of missing energy searches. We begin with a brief discussion of the utility and limitation of the effective field theory approach to this problem. The bulk of the report is then devoted to several different simplified models and their signatures, including s-channel and t-channel processes. A common feature of simplified models for DM is the presence of additional particles that mediate the interactions between the Standard Model and the particle that makes up DM. We consider these in detail and emphasize the importance of their inclusion as final states in any coherent interpretation. We also review some of the experimental progress in the field, new signatures, and other aspects of the searches themselves. We conclude with comments and recommendations regarding the use of simplified models in Run-II of the LHC.Comment: v2. references added, version submitted to journal. v1. 47 pages, 13 plot

Morpho-structural alterations of sub-chondral bone tissue in patients with osteoarthritis: a scanning electron microscopy study

Osteoarthritis focuses principally on the degeneration of articular cartilage as a primary cause of the disease. The pathophysiological process of osteoarthritis is characterized by alteration of chondrocytes and the increased bone formation by sub-chondral osteoblasts. Infiltration of macrophages and perivascular T and B lymphocytes is observed, and these infiltrates have been demonstrated in both early and advanced disease. The morphological and phenotypic characteristics of osteocytic cells attached to the normal and the osteoarthritic matrix differ from each other, suggesting that specific signalling pathways arise or are altered between matrix and cells. On this basis, we have examined biopsies of bone obtained by normal femur and by femur of subjects affected by osteoarthritis using techniques of scanning electron microscopy in order to identify the morphostructural alterations that occur in the sub-chondral bone. Our results have shown that the bone tissue of subjects not affected by any disease of bone presents a well-organized structure, while the bone tissue obtained by patients affected by osteoarthritis shows a derangement of tissue itself possibly correlated with altered function of the osteoblasts, that during the pathological process produce a less mineralized extracellular matrix with consequent loss of the normal bone structure. In our opinion, during the osteoarthritic process there would be a defective signalling between bone cells leading to the production of an irregular, amorphous extracellular matrix by osteoblasts, characteristic of the pathological condition