Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis

Erythropoietin (EPO) is of great interest as a therapy for many of the central nervous system (CNS) diseases and its administration is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Endogenous EPO is induced by hypoxic/ischemic injury, but little is known about its expression in other CNS diseases. We report here that EPO expression in the spinal cord is induced in mouse models of chronic or relapsing-remitting EAE, and is prominently localized to motoneurons. We found a parallel increase of hypoxia-inducible transcription factor (HIF)-1 alpha, but not HIF-2 alpha, at the mRNA level, suggesting a possible role of non-hypoxic factors in EPO induction. EPO mRNA in the spinal cord was co-expressed with interferon (IFN)-gamma and tumor necrosis factor (TNF), and these cytokines inhibited EPO production in vitro in both neuronal and glial cells. Given the known inhibitory effect of EPO on neuroinflammation, our study indicates that EPO should be viewed as part of the inflammatory/anti-inflammatory network in MS

Моделирование магнетронной распылительной системы методом конечных элементов

В работе проведено моделирование магнетронной распылительной системы методом конечных элементов и методом Галеркина. Получены распределения концентрации и скоростей носителей заряда, распределение электрического потенциала и магнитного поля, рассмотрены временные зависимости физических величин. Разработано программное обеспечение для моделирования сложных физических задач. Проведена верификация расчетного алгоритма на примере решения модельных задач. Отличительной особенностью исследуемой модели от существующих является учет нестационарного и конвективного слагаемых в уравнении для переноса скорости электрона и максимально точная реализация всех слагаемых в дифференциальном уравнении (в рамках метода Галеркина).The dissertation examines the modeling of a magnetron sputtering system by finite element analysis and Galerkin method. The model makes it possible to calculate the concentration, velocity, temperature, electrical potential and magnetic field. The methods and the code developed according to the model are usable for modeling complex physical tasks. The work also includes analysis and verification of results

Chemometric-assisted cocrystallization: Supervised pattern recognition for predicting the formation of new functional cocrystals

Owing to the antimicrobial and insecticide properties, the use of natural compounds like essential oils and their active components has proven to be an effective alternative to synthetic chemicals in different fields ranging from drug delivery to agriculture and from nutrition to food preservation. Their limited application due to the high volatility and scarce water solubility can be expanded by using crystal engineering approaches to tune some properties of the active molecule by combining it with a suitable partner molecule (coformer). However, the selection of coformers and the experimental effort required for discovering cocrystals are the bottleneck of cocrystal engineering. This study explores the use of chemometrics to aid the discovery of cocrystals of active ingredients suitable for various applications. Partial Least Squares–Discriminant Analysis is used to discern cocrystals from binary mixtures based on the molecular features of the coformers. For the first time, by including failed cocrystallization data and considering a variety of chemically diverse compounds, the proposed method resulted in a successful prediction rate of 85% for the test set in the model validation phase and of 74% for the external test set

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

CircRNAs constitute a novel class of RNA, generally considered as non-coding RNAs; nonetheless, their coding potential has been under scrutiny. In this work, we systematically explored the predicted proteins of more than 160,000 circRNAs detected by exome capture RNA-sequencing and collected in the MiOncoCirc pan-cancer compendium, including normal and cancer samples from different types of tissues. For the functional evaluation, we compared their primary structure and domain composition with those derived from the same linear mRNAs. Among the 4362 circRNAs potentially encoding proteins with a unique primary structure and 1179 encoding proteins with a novel domain composition, 183 were differentially expressed in cancer. In particular, eight were associated with prognosis in acute myeloid leukemia. The functional classification of the dysregulated circRNA-encoded polypeptides showed an enrichment in the heme and cancer signaling, DNA-binding, and phosphorylation processes, and disclosed the roles of some circRNA-based effectors in cancer

The "Defibrillation Testing, Why Not?" survey. Testing of subcutaneous and transvenous defibrillators in the Italian clinical practice

Background: Defibrillation testing (DT) can be omitted in patients undergoing transvenous implantable cardioverter-defibrillator (T-ICD) implantation, but it is still recommended for patients at risk for a high defibrillation threshold and for ICD generator changes. Moreover, DT is still recommended on implantation of subcutaneous ICD (S-ICD). The aim of the present survey was to analyze the current practice of DT during T-ICD and S-ICD implantations.Methods: In March 2021, an ad hoc questionnaire on the current performance of DT and the standard practice adopted during testing was completed at 72 Italian centers implanting S-ICD and T-ICD.Results: 48 (67%) operators reported never performing DT during de-novo T-ICD implantations, while no operators perform it systematically. The remaining respondents perform it for patients at risk for a high defibrillation threshold. DT is never performed at T-ICD generator change. At the time of de-novo S-ICD implantation, DT is never performed by 9 (13%) operators and performed systematically by 48 (66%). The remaining operators frequently omit DT in patients with more severe systolic dysfunction. DT is not performed at S-ICD generator change by 92% of operators. DT is conducted by delivering a first shock energy of 65 J by 60% of operators, while the remaining 40% test lower energy values.Conclusions: In current clinical practice, most operators omit DT at T-ICD implantation, even when still recommended in the guidelines. DT is also frequently omitted at S-ICD implantation, and a wide variability exists among operators in the procedures followed during DT

Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection

IntroductionProstate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters.MethodsWe included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated.ResultsForty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen’s kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen’s kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively).ConclusionsWe found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score

Safety and efficacy of totally minimally invasive right colectomy in the obese patients: a multicenter propensity score-matched analysis

Despite the well-known benefits of the minimally invasive approach for the right colon cancer treatment, less is known about its feasibility and advantages in morbid obese patients. The aim of this study is to compare the postoperative outcomes after totally minimally invasive right colectomy between the obese and non-obese population. Data derived from a prospectively maintained multicenter colorectal database were analysed, dividing the enrolled patients into two groups: obese (BMI > 29.99) patient group and non-obese patient group. Data about gender, age, American Society of Anesthesiologists (ASA) Score, tumor characteristics, operative time, anastomosis time, extraction site, incision length, intraoperative complications, postoperative complications, postoperative recovery, specimen length and retrieved nodes were taken to assess the achievement of the oncologic standards. After a propensity score matching, a total of 184 patients was included, 92 in each group. No differences were found in terms of demographic data and tumor characteristics. Intraoperative data showed a significant difference in terms of anastomosis time in favour of non-obese group (p < 0.0001). No intraoperative complications were recorded and no conversion was needed in both groups. No differences were found in terms of postoperative complications. There were no differences in terms of first mobilization (p = 0.745), time to first flatus (p = 0.241) time to tolerance to liquid and solid diet (p = 0.241 and p = 0.06) and length of hospital stay (p = 0.817). The analysis of oncologic outcomes demonstrated adequate results in both groups. The results obtained by our study confirmed the feasibility and safety of the totally minimally invasive approach even in obese population