3D-QSAR Study of New Acetyl-COA:Cholesterol O-Acyl Transferase (ACAT) Inhibitors

3D QSAR models using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) were built on a training set of 19 previously described inhibitors of acetyl-CoA:cholesterol O-acyl transferase (ACAT) with a IC50 ranging from 47 nM to 200 µM. The models thus obtained were found to be predictive as shown by correct prediction of the inhibitory activity of a set of recently published compounds

Un'applicazione della Social Network Analisys alla rete di relazioni di un Gruppo d’Acquisto Solidale: l’esperienza di Gasualmente

The phenomenon of GAS (Solidarity Purchase Groups) in Sicily has in Gasualmente an important actor. This GAS, was created following a structured training program and research by the Faculty of Agriculture of the University of Palermo. It now plays an important role as activator of relationships and ethical affirmation of critical consumption, and promotion of organic products. The study aims through the Social Network Analysis, to investigate Gasualmente network and the role played by all the actors involved

Insights into the Mind of a Trojan Designer: The Challenge to Integrate a Trojan into the Bitstream

The threat of inserting hardware Trojans during the design, production, or in-field poses a danger for integrated circuits in real-world applications. A particular critical case of hardware Trojans is the malicious manipulation of third-party FPGA configurations. In addition to attack vectors during the design process, FPGAs can be infiltrated in a non-invasive manner after shipment through alterations of the bitstream. First, we present an improved methodology for bitstream file format reversing. Second, we introduce a novel idea for Trojan insertion

Perceived public stigma towards schizophrenia among healthcare students: The relationship with diagnostic labelling and contact with people with schizophrenia

Objectives This study aimed at investigating the relationship between perceived public stigma towards people with schizophrenia (PWS) and their family members in a large sample of medical and psychology students. We hypothesised that: a) schizophrenia labelling would be related to greater perceived public stigma; b) contact with PWS would be related with lower perceived stigma; c) perceived public stigma would be similar between medical and psychology students and would be higher among students attending the clinical stage compared to their pre-clinical colleagues. Methods Participants were 592 students attending either the pre-clinical or clinical stage of coursework in Medicine and Psychology, at the University of Palermo (Italy) (Tab. I). Study measures included a short socio-demographic questionnaire, the Devaluation of Consumers Scale (DCS), and the Devaluation Consumers Families Scale (DCFS). Results Students who identified schizophrenia in an unlabelled clinical description expressed greater perceived public stigma towards PWS (t = -2.895, p = 0.004) and their family members (t = -2.389, p = 0.017). A trend-level association was found between previous contact with PWS and lower perceived public stigma (t = 1.903, p = 0.058), which became significant for those students who had a more extensive contact (Mann-Whitney z = 2.063, p = 0.039). Compared to medical students, psychology students perceived greater public stigma towards PWS. No difference was observed between students at different stages of their academic coursework (Tab. II). In a multivariate linear regression model, schizophrenia labelling and degree course predicted perceived public stigma towards severe mental disorders. Conclusions This study replicated previous findings on the relationship between public stigma towards PWS, schizophrenia labelling, and contact with PWS. Perception of public stigma was similar among pre-clinical and clinical students and greater among psychology students. The findings suggest the importance of promoting a critical awareness of negative stereotypes towards schizophrenia among healthcare students, since the beginning of their coursework. In addition to correct information about schizophrenia, anti-stigma intervention should include contact with PWS who live in the community

Endurance training damages small airway epithelium in mice.

RATIONALE: In athletes, airway inflammatory cells were found to be increased in induced sputum or bronchial biopsies. Most data were obtained after exposure to cold and dry air at rest or during exercise. Whether training affects epithelial and inflammatory cells in small airways is unknown. OBJECTIVES: To test whether endurance training under standard environmental conditions causes epithelial damage and inflammation in the small airways of mice. METHODS AND MEASUREMENTS: Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n = 14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and 45 days of training. The following variables were assessed (morphometry and immunohistochemistry) in small airways (basement membrane length < 1 mm): (1) integrity, proliferation, and apoptosis of bronchiolar epithelium; and (2) infiltration, activation, and apoptosis of inflammatory cells. MAIN RESULTS: Compared with sedentary mice, bronchiolar epithelium of trained mice showed progressive loss of ciliated cells, slightly increased thickness, unchanged goblet cell number and appearance, and increased apoptosis and proliferation (proliferating cell nuclear antigen) (p < 0.001 for all variables). Leukocytes (CD45(+) cells) infiltrated airway walls (p < 0.0001) and accumulated within the lumen (p < 0.001); however, apoptosis of CD45(+) cells did not differ between trained and sedentary mice. Nuclear factor-kappaB translocation and inhibitor-alpha of NF-kappaB (IkappaBalpha) phosphorylation were not increased in trained compared with sedentary mice. CONCLUSIONS: Bronchiolar epithelium showed damage and repair associated with endurance training. Training increased inflammatory cells in small airways, but inflammatory activation was not increased. These changes may represent an adaptive response to increased ventilation during exercise

Using machine learning to characterize heart failure across the scales

Heart failure is a progressive chronic condition in which the heart undergoes detrimental changes in structure and function across multiple scales in time and space. Multiscale models of cardiac growth can provide a patient-specific window into the progression of heart failure and guide personalized treatment planning. Yet, the predictive potential of cardiac growth models remains poorly understood. Here, we quantify predictive power of a stretch-driven growth model using a chronic porcine heart failure model, subject-specific multiscale simulation, and machine learning techniques. We combine hierarchical modeling, Bayesian inference, and Gaussian process regression to quantify the uncertainty of our experimental measurements during an 8-week long study of volume overload in six pigs. We then propagate the experimental uncertainties from the organ scale through our computational growth model and quantify the agreement between experimentally measured and computationally predicted alterations on the cellular scale. Our study suggests that stretch is the major stimulus for myocyte lengthening and demonstrates that a stretch-driven growth model alone can explain 52.7% of the observed changes in myocyte morphology. We anticipate that our approach will allow us to design, calibrate, and validate a new generation of multiscale cardiac growth models to explore the interplay of various subcellular-, cellular-, and organ-level contributors to heart failure. Using machine learning in heart failure research has the potential to combine information from different sources, subjects, and scales to provide a more holistic picture of the failing heart and point toward new treatment strategies

Life-saving vascular access after combined liver and kidney transplantation: A challenging access to the right atrium

Exhaustion of vascular accesses is a major complication in patients undergoing hemodialysis, especially in pediatric setting. We report the case of a boy treated for loss of hemodialysis access after a combined liver-kidney transplantation and transient renal dysfunction. An interventional dilatation of calcific superior vena cava allowed to insert a stable central venous line for dialysis until full graft recovery. Careful management of central lines allows to spare the main vessels and reduces the need for unusual accesses

Quantitative comparison of myocardial fiber structure between mice, rabbit, and sheep using diffusion tensor cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Accurate interpretations of cardiac functions require precise structural models of the myocardium, but the latter is not available always and for all species. Although scaling or substitution of myocardial fiber information from alternate species has been used in cardiac functional modeling, the validity of such practice has not been tested.</p> <p>Methods</p> <p>Fixed mouse (n = 10), rabbit (n = 6), and sheep (n = 5) hearts underwent diffusion tensor imaging (DTI). The myocardial structures in terms of the left ventricular fiber orientation helix angle index were quantitatively compared between the mouse rabbit and sheep hearts.</p> <p>Results</p> <p>The results show that significant fiber structural differences exist between any two of the three species. Specifically, the subepicardial fiber orientation, and the transmural range and linearity of fiber helix angles are significantly different between the mouse and either rabbit or sheep. Additionally, a significant difference was found between the transmural helix angle range between the rabbit and sheep. Across different circumferential regions of the heart, the fiber orientation was not found to be significantly different.</p> <p>Conclusions</p> <p>The current study indicates that myocardial structural differences exist between different size hearts. An immediate implication of the present findings for myocardial structural or functional modeling studies is that caution must be exercised when extrapolating myocardial structures from one species to another.</p

Статеві особливості метаболізму міокарда в динаміці розвитку експериментального гіпертиреозу

В экспериментах на половозрелых самцах и самках крыс исследовано активность перекисного окислення липидов, антиоксидантной защиты и энергообразования в динамике развития тироксиновой кардиомиопатии, которую моделировали введением L-тироксина (500 мг/кг, внутрижелудочно, ежедневно). В миокарде желудочков через 5, 10 и 15 дней с начала эксперимента определяли содержание диеновых и триеновых коньюгат (ДК, ТК), ТБК-активных продуктов (ТБК-АП), активность супероксиддисмутазы (СОД), каталазы, глутатионпероксидазы (ГП) и глутатионредуктазы (ГР), сукцинатдегидрогеназы (СДГ), цитохромоксидазы (ЦО). Установили, что гипертироксинемия визывала накопление в миокарде желудочков крыс ДК, ТК и ТБК-АП, что в самок было более существенным, чем у самцов, несмотря на большую активность ГП та ГР. Недостаточная протекторная эффективность ферментов системы глутатиона была результатом значительного угнетения активности СОД и каталазы, что свидетельствовало о существенном накоплении активных форм кислорода. Активность энергообразования в таких условиях уменьшалась, о чем свидетельствовало угнетение активности СДГ, которое было аналогичным в самцов и самок, и ЦО, что было более существенным в самок. Полученные результаты свидетельствуют о том, что развитие тироксиновой кардиомиопатии вызывает существенный метаболический дисбаланс в миокарде желудочков самок крыс, что разрешает ожидать болем интенсивные структурные нарушения.Lipid peroxidation, antioxidant protection and energy production were studied in adult male and female rats with thyroxin cardiomyopathy, which simulated by introduction of L-thyroxine (500 mg / kg, intraperitoneally, daily). In the myocardium of the ventricles after 5, 10 and 15 days from the start of the experiment determined the content of diene and triene conjugate (DC, TC), TBA-active metabolits (TBA-am), activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GP) and glutathione reductase (GR), succinate dehydrogenase (SDH), cytochrome oxidase (CO). Found that hyperthyroxinemia caused accumulation in myocardium of the ventricles DC, TC and TBA-am mostly in females despite the higher activity of GP and GR. Lack of protective effects of glutathione system enzymes resulted from significant inhibition of SOD and catalase, indicating a significant accumulation of reactive species of oxygen. Activity of the energy production in these conditions decreased. That was proved by the inhibition of SDH in myocardium both sex animals and CO mostly in females. We conclude that the development of thyroxin cardiomyopathy causes metabolic disbalance in myocardium of the ventricles mostly in female rats, which can results in more intense structural damage