Investigation on Quantitative Structure-Activity Relationships of 1,3,4 Oxadiazole Derivatives as Potential Telomerase Inhibitors

The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/164022/article, DOI : 10.2174/1570163815666180724113208. © 2018 Bentham ScienceA series of 1,3,4-oxadiazole derivatives with significant broad-spectrum anticancer activity against different cell lines, and demonstrated telomerase inhibition, was subjected to Quantitative Structure-Activity Relationships (QSAR) analysis. Validated models with high correlation coefficients were developed. The Multiple Linear Regression (MLR) models, by Ordinary Least Squares (OLS), showed good robustness and predictive capability, according to the Multi-Criteria Decision Making (MCDM = 0.8352), a technique that simultaneously enhances the performances of a certain number of criteria. The descriptors selected for the models, such as electrotopological state (E-state) descriptors, and extended topochemical atom (ETA) descriptors, showed the relevant chemical information contributing to the activity of these compounds. The results obtained in this study make sure about the identification of potential hits as prospective telomerase inhibitors.Peer reviewedFinal Accepted Versio

Predicting Skin Permeability by means of Computational Approaches : Reliability and Caveats in Pharmaceutical Studies

© 2019 American Chemical Society.The skin is the main barrier between the internal body environment and the external one. The characteristics of this barrier and its properties are able to modify and affect drug delivery and chemical toxicity parameters. Therefore, it is not surprising that permeability of many different compounds has been measured through several in vitro and in vivo techniques. Moreover, many different in silico approaches have been used to identify the correlation between the structure of the permeants and their permeability, to reproduce the skin behavior, and to predict the ability of specific chemicals to permeate this barrier. A significant number of issues, like interlaboratory variability, experimental conditions, data set building rationales, and skin site of origin and hydration, still prevent us from obtaining a definitive predictive skin permeability model. This review wants to show the main advances and the principal approaches in computational methods used to predict this property, to enlighten the main issues that have arisen, and to address the challenges to develop in future research.Peer reviewedFinal Accepted Versio

Synthesis and cytotoxic activity of 3-[2-(1H-Indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[3,2-c]pyridine hydrobromides, analogues of the marine alkaloid nortopsentin

A new series of thiazole nortopsentin analogues with a 5-azaindole moiety was conveniently synthesized in good to excellent yields by an Hantzsch reaction between thioamides and \u3b1-bromoacetyl compounds. The cytotoxic activity of the new derivatives was tested against different human tumor cell lines of the NCI full panel. All tested compounds were active against all of the investigated cell lines showing GI50 values from micro to submicromolar levels. Some of the new analogues exhibited good selectivities against different NCI sub-panels

Canning Processes Reduce the DNA-Based Traceability of Commercial Tropical Tunas

Canned tuna is one of the most widely traded seafood products internationally and is of growing demand. There is an increasing concern over the vulnerability of canned tuna supply chains to species mislabelling and fraud. Extensive processing conditions in canning operations can lead to the degradation and fragmentation of DNA, complicating product traceability. We here employed a forensically validated DNA barcoding tool (cytochrome b partial sequences) to assess the effects of canning processes on DNA degradation and the identification of four tropical tuna species (yellowfin, bigeye, skipjack and longtail tuna) collected on a global scale, along their commercial chains. Each species was studied under five different canning processes i.e., freezing, defrosting, cooking, and canning in oil and brine, in order to investigate how these affect DNA-based species identification and traceability. The highest percentage of nucleotide substitutions were observed after brine-canning operations and were greatest for yellowfin and skipjack tuna. Overall, we found that DNA degradation significantly increased along the tuna canning process for most specimens. Consequently, most of the specimens canned in oil or brine were misidentified due to the high rate of nucleotide substitution in diagnostic sequences

The Wellbeing of Priests in the Time of COVID‑19 Illness Pandemics

Svećenici su se također za vrijeme pandemije bolesti COVID‑19 suočili s novim načinom življenja vlastitog poslanja i poziva, tim više što je svećeničko poslanje usmjereno najčešće na živi kontakt s ljudima. Uzeli smo u obzir odnos svećenika prema drugima, prema sebi i prema Bogu. U istraživanju, koje je provedeno od kraja studenoga do polovice prosinca 2020. godine, sudjelovalo je 312 svećenika, redovnika i dijecezanskih svećenika, koji žive i rade u Hrvatskoj, Bosni i Hercegovini, Srbiji te jedan manji dio u ostalim državama. Za potrebe istraživanja korišteni su upitnici, prevedeni prema novim standardima prevođenja, kojima se ispitivalo psihološko blagostanje svećenika, suosjećanje i samo‑suosjećanje te je prigodni upitnik pripremljen za potrebe ovog istraživanja koji je u fokusu imao pastoralni život svećenika za vrijeme pandemije bolesti COVID‑19. Veći broj svećenika, to jest 77 %, izjavio je kako su u doba pandemije odvojili više vremena za molitvu nego uobičajeno, što je ujedno i povezano s većim osobnim rastom i pozitivnim odnosima s drugima. Materijalne poteškoće imali su svećenici koji žive i djeluju u župama manjim od 3000 stanovnika. Ističe se kako nema značajnijih razlika u psihološkoj dobrobiti (psychological well‑being) između dijecezanskih svećenika i redovnika kao ni između svećenika koji žive sami ili u zajednici s drugim svećenicima. Primijetili smo značajne razlike u brizi o sebi kod svećenika koji su na službi duže od dvadeset godina života, gdje upravo oni pokazuju višu razinu brige o sebi. Na koncu, značajnim se pokazalo da oni svećenici koji su više suosjećajni prema samima sebi, imaju i višu razinu psihološke dobrobiti.The priest also had to deal with a new way of living their own vocation and mission during the time of COVID‑19 illness pandemics, especially since their mission is most often realized through personal contact with people. The author takes into account the relation of priests towards others, towards themselves, and towards God. In the study that has been carried out from the end of November until the first half of December of 2020, 312 priests, religious order and diocesan priests, who live and work in Croatia, Bosnia and Herzegovina, Serbia, and a small number of those in other countries, took part. For the purposes of the study, questionnaires were used that were translated according to the new standards of translation and that measured the psychological wellbeing of priests, compassion, and compassion towards oneself. On the basis of that, an appropriate questionnaire was prepared for the purposes of this study that focused on the pastoral life of priests during the COVID‑19 illness pandemics. The majority of priests, more precisely 77%, stated that they used more time than usual for prayer, which is also related to a more significant personal growth and positive relationships with others. The priests who live in parishes that have less than 3000 inhabitants, however, faced financial difficulties. The study also marked that there were no significant differences in psychological wellbeing between diocesan priests and priests in religious orders, as well as between those priests who live alone and those who live in a community with other priests. The study did mark significant differences in the care for oneself among those priests who have been active in the office for more than twenty years and who show more awareness for the importance of caring for oneself. Finally, it has been shown that those priests who are more compassionate towards themselves, also exhibit a higher level of psychological wellbeing

Diagnostics for the knowledge: the case of the tower of Palazzo Termine Pietragliata in Palermo (Italy)

[EN] Developing a methodological approach is crucial to assess the state of conservation of a monument, starting from the overall analysis, progressively moving from small to medium scale and reaching the grand scale at the end. Considering the territory, causes are investigated in order to understand the propensities, as well as considering a single monument, evidences are carefully read to assess the overall conditions, that will be lately detailed by the analysis on materials and their degradation. The object of this study is the tower of the Palazzo Pietragliata in Palermo, one of the most important examples of the late Gothic civil architecture in Sicily. The Palace, built in 1473 by Prince of Baucina, possesses an imposing crenellated tower, whose two levels are connected by an original internal staircase “cargol” like, an extraordinary example of the influence of Catalan Gothic architecture in Sicily. Some micro samples were taken from the tower structure, made entirely of blocks of biocalcarenite, on which diagnostic investigations were performed in the laboratory. In the context of a more comprehensive interdisciplinary study, this paper illustrates the specific results of the micro analysis conducted in the laboratory and particularly those made through the use of the SEM and biological investigations, also paying attention to the pathologies detected on the battlements of the tower. These forms of decay, for their variety, represent a significant example that allows to properly illustrate the adopted study method.Gattuso, C.; Fernandez, F.; Pecoraro, MM.; Palermo, AM. (2015). Diagnostics for the knowledge: the case of the tower of Palazzo Termine Pietragliata in Palermo (Italy). En Defensive architecture of the mediterranean: XV to XVIII centuries. Vol. I. Editorial Universitat Politècnica de València. 389-396. https://doi.org/10.4995/FORTMED2015.2015.1760OCS38939

QT Indexes in Cirrhotic Patients: Relationship with Clinical Variables and Potential Diagnostic Predictive Value.

BACKGROUND AND AIMS: A wide spectrum of cardiovascular changes characterizes cirrhosis, ranging from subclinical alterations to hyperkinetic syndrome. We looked for ECG markers of ventricular repolarization in a population of patients with cirrhosis in comparison to patients without cirrhosis and we investigated the relationship between these and other clinical and laboratory variables. METHODS: In 149 patients with cirrhosis and 152 controls, we measured QT maximum interval (QTmax), QT corrected interval (QTc), QT minimum interval (QTmin), QT dispersion (QTdisp), QT peak and T peak-to-end (TpTe). RESULTS: In subjects with cirrhosis, in comparison with controls, we observed a higher mean QTmax, mean QTc, mean QTmin, mean QTdisp and mean TpTe. At Cox regression analysis, diastolic blood pressure and beta-blocker treatment were significantly associated with mean QTmax, hypertension with mean QTmin and mean QTc, diastolic blood pressure, beta-blockers and ACE-inhibitors/ARBs with QT disp, and beta-blockers with TpTe. Analysis of ROC curves showed a significant area under curve towards cirrhosis diagnosis, respectively, for a cut-off value of >400 msec of QTmax, >360 msec of QTmin, >450 msec of QTc, >105 msec of TpTe and >55 msec of QTdisp

Treatment of de novo femoro-popliteal lesions with a new Drug Coated Balloon: early experience of a single Center in the first 50 patients

Angioplasty with drug-coated balloon (DCB) is an emerging and reliable method for the treatment of femoro-popliteal lesions. We report our experience with the Stellarex™ DCB in the first 50 patients. Methods - From July 2015 to November 2017, 50 patients (41 M, 9F), medium age (64 ± 7.4 year) were subject to 33 angioplasties (PTAs) for femoro-popliteal lesions with a paclitaxel-coated balloon (Stellarex™). Based upon clinical data sixteen patients had severe claudication (56% - Rutherford class 3); ten patients suffered from ischemic rest pain (34% - Rutherford class 4); and five presented minor tissue loss (10% - Rutherford class 5). 42% of patients showed femoro-popliteal lesion TASC-II B, and 58% presented lesions pertaining to TASC-II C. Results - Immediate technical success was 100% without perioperative complications. Primary patency rate was 94% at twelve months. In three cases restenosis (6%) was detected within a year from procedure, and a further PTA DCB was performed with primary assisted patency rates of 100% at twelve months. Two patients underwent major lower limb amputation. Three patients died during follow-up and one patient was lost at follow-up. Conclusion - DCB angioplasty with Stellarex™ is a viable alternative to traditional endovascular procedures proving satisfactory primary patency rates at twelve months. Based on our experience, treatment with DCB is a first choice technique for non-complex de novo lesions of the femoro – popliteal tract

HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute viral encephalitis

Introduction: The HLA genes, as well as the innate immune KIR genes, are considered relevant determinants of viral outcomes but no study, to our knowledge, has evaluated their role in the clinical setting of acute viral encephalitis. Results: Subjects with acute viral encephalitis in comparison to subjects without acute viral encephalitis showed a significantly higher frequency of 2DL1 KIR gene and AA KIR haplotypes and of HLA-C2 and HLA-A-Bw4 alleles. Subjects without acute viral encephalitis showed a higher frequency of interaction between KIR2DL2 and HLAC1. Multiple logistic regression analysis showed the detrimental effect of HLA-A haplotype and HLA-C1, HLA-A-BW4 HLA-B-BW4T alleles, whereas multiple logistic regression showed a protective effect of AB+BB KIR haplotype and a detrimental effect of interaction between KIR3DL1 and HLA-A-Bw4. Discussion: Our findings of a lower frequency of activating receptors in patients with acute encephalitis compared to controls could result in a less efficient response of NK cells. This finding could represent a possible pathogenetic explanation of susceptibility to acute symptomatic encephalitis in patients with viral infection from potentially responsible viruses such as Herpes virus. Materials and Methods: 30 Consecutive patients with symptomatic acute viral encephalitis and as controls, 36 consecutive subjects without acute encephalitis were analyzed. The following KIR genes were analyzed, KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 3DL2, 3DL3, 2DL4, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1, 2 pseudogenes (2DP1 and 3DP1) and the common variants of KIR2DL5 (KIR2DL5A, KIR2DL5B)