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

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

Caratterizzazione della dinamica produttiva di pascoli naturali italiani

This work studies herbage production and its seasonal distribution in indigenous pastures, and analyses the relationship between the environmental factors (soil, clima, vegetation) and the productivity of these resources. The investigations have been carried on during the period 1983-90 by the joint activity of 10 different University Istitutions in 23 different environments distributed along the Italian peninsula and the main islands. For each environment, pasture production has been measured with the Corrall and Fenlon method, analysing the more important vegetational and ecological conditions; altogether the total yearly production and the seasonal pattern of herbage production have been detected on 104 pastures. The total herbage yield is not significantly influenced by the latitudinal gradient, and the overall regional (alps, central Appenine, south Apennine and islands) production is about 2.3 t ha-1 year-1 The wide range (0.5-6.3 t ha-1 year-1) of herbage production, on small or medium scale, seems to be due to evident changeof environmental or management factors. Five types of seasonal distribution of herbage growth are evidenced with multivariate analysis methods, based on the growing season and the amplitude of the growth. With mean temperature above 12°C and total rainfall below 800 mm, herbage distribution shows a standstill during summer period and an evident regrowth in autumn. On the contrary, for the 4 other distribution types, the winter standstill become important, and the types are distinct by summer growth amplitude and by the growing season lenght. With cluster analysis method, for each type of herbage distribution, have been pointed out under-types characterized by interannual herbage production variation. Among the environmental factors, vegetation characheristics, expressed as Pasture Value following Daget and Poissonet seems to be strictly correlated with total production. The comparative poor role played by the soil and climatic factor, may be due to the strong past and present antropic influence, related with management and utilization techniques. Il presente lavoro ha come scopo l'approfondimento delle conoscenze sulla produzione e sulla distribuzione stagionale della crescita dell'erba dei pascoli naturali, nonché l'analisi delle interazioni tra i fattori ambientali, pedo-climatici e vegetazionali, e la risposta produttiva di queste risorse. La ricerca è stata condotta nel periodo 1983-90 da 10 diverse Istituzioni Universitarie, in 23 ambienti differenti, distribuiti lungo tutta la penisola e le isole maggiori. Per ogni ambiente, con il metodo di rilievo di Corrall e Fenlon, è stata saggiata la risposta produttiva di pascoli rappresentativi delle principali situazioni vegetazionali e di giacitura; complessivamente sono state rilevate la produzione totale annua e la curva di produttività media pluriennale di 104 pascoli. Riguardo la produzione annua complessiva si è osservato che essa non presenta variazioni significative lungo il gradiente latitudinale, collocandosi tra le diverse regioni (alpina, centro appenninica, suq, appenninica e insulare) attorno a 2.3 t ha-1 anno-1. La fitomassa raccolta è soggetta invece a variazioni sensibili (0.5-6.3 t ha-1 anno-1) riconducibili a fattori ambientali e gestionali che si esprimono su piccola e media scala. Con metodi di analisi multivariata si sono individuate 5 tipologie distributive della crescita dell'erba, in rapporto alla stagione vegetativa e alle variazioni dell'intensità di crescita nel corso della stagione stessa. Con temperature medie e precipitazioni annue rispettivamente maggiori di 12°C e minori di 800 mm, risulta evidente la stasi vegetativa nel trimestre estivo e la ripresa vegetativa autunnale. Nel caso opposto la stasi è invernale e le 4 tipologie afferenti a questo modello, sono distinguibili dall'entità della crescita nei mesi estivi e dalla durata della stagione vegetativa. Per ogni tipologia produttiva, sono state evidenziate, tramite l'analisi cluster, sotto-tipologie distinte per la variabilità produttiva interannuale. Tra i fattori ambientali, la vegetazione, espressa attraverso l'indice del valore pastorale di Daget e Poissonet, presenta una buona capacità predittiva nei confronti del livello produttivo dei pascoli. Il contributo comparativamente modesto offerto dai fattori pedoclimatici sembra attribuibile alla forte influenza antropica, pregressa e attuale, attraverso le cure colturali e l'utilizzazione