Pinus mugo essential oil impairs STAT3 activation through oxidative stress and induces apoptosis in prostate cancer cells

Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy

Intraoperative Defibrillation Testing of Subcutaneous Implantable Cardioverter‐Defibrillator Systems—A Simple Issue?

Background: The results of the recently published randomized SIMPLE trial question the role of routine intraoperative defibrillation testing. However, testing is still recommended during implantation of the entirely subcutaneous implantable cardioverter‐defibrillator (S‐ICD) system. To address the question of whether defibrillation testing in S‐ICD systems is still necessary, we analyzed the data of a large, standard‐of‐care prospective single‐center S‐ICD registry. // Methods and Results: In the present study, 102 consecutive patients received an S‐ICD for primary (n=50) or secondary prevention (n=52). Defibrillation testing was performed in all except 4 patients. In 74 (75%; 95% CI 0.66–0.83) of 98 patients, ventricular fibrillation was effectively terminated by the first programmed internal shock. In 24 (25%; 95% CI 0.22–0.44) of 98 patients, the first internal shock was ineffective and further internal or external shock deliveries were required. In these patients, programming to reversed shock polarity (n=14) or repositioning of the sensing lead (n=1) or the pulse generator (n=5) led to successful defibrillation. In 4 patients, a safety margin of <10 J was not attained. Nevertheless, in these 4 patients, ventricular arrhythmias were effectively terminated with an internal 80‐J shock. // Conclusions: Although it has been shown that defibrillation testing is not necessary in transvenous ICD systems, it seems particular important for S‐ICD systems, because in nearly 25% of the cases the primary intraoperative test was not successful. In most cases, a successful defibrillation could be achieved by changing shock polarity or by optimizing the shock vector caused by the pulse generator or lead repositioning.<br

Migration, communities-on-the-move and international innovation networks: An empirical analysis of Spanish regions

This paper investigates the impact of migration on innovation networks between regions and foreign countries. We posit that immigrants (emigrants) act as a transnational knowledge bridge between the host (home) regions and their origin (destination) countries, thus facilitating their co-inventorship networks. We also argue that the social capital of both the hosting and the moving communities reinforces such a bridging role, along with language commonality and migrants’ human capital. Focusing on Spain, as a country that hosted an intense process of migration over the past two decades, we combine patent data with national data on residents and electors abroad and we apply a gravity model to the co-inventorship between Spanish provinces (NUTS3 regions) and a number of foreign countries. Both immigrants and emigrants affect the kind of innovation networking at stake. The social capital of both the moving and the hosting communities actually moderate this impact in a positive way. The effect of migration is stronger for more skilled migrants and with respect to non-Spanish speaking countries, pointing to a language-bridging role of migrants. Policy implications are drawn accordingly

IFRD1 gene polymorphisms are associated with nasal polyposis in cystic fibrosis patients

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Equilibrium and dynamical properties of two dimensional self-gravitating systems

A system of N classical particles in a 2D periodic cell interacting via long-range attractive potential is studied. For low energy density $U$ a collapsed phase is identified, while in the high energy limit the particles are homogeneously distributed. A phase transition from the collapsed to the homogeneous state occurs at critical energy U_c. A theoretical analysis within the canonical ensemble identifies such a transition as first order. But microcanonical simulations reveal a negative specific heat regime near $U_c$. The dynamical behaviour of the system is affected by this transition : below U_c anomalous diffusion is observed, while for U > U_c the motion of the particles is almost ballistic. In the collapsed phase, finite $N$-effects act like a noise source of variance O(1/N), that restores normal diffusion on a time scale diverging with N. As a consequence, the asymptotic diffusion coefficient will also diverge algebraically with N and superdiffusion will be observable at any time in the limit N \to \infty. A Lyapunov analysis reveals that for U > U_c the maximal exponent \lambda decreases proportionally to N^{-1/3} and vanishes in the mean-field limit. For sufficiently small energy, in spite of a clear non ergodicity of the system, a common scaling law \lambda \propto U^{1/2} is observed for any initial conditions.Comment: 17 pages, Revtex - 15 PS Figs - Subimitted to Physical Review E - Two column version with included figures : less paper waste

Miglioramento della resistenza e della performance muscolare mediante trattamento con onde d&#8217;urto defocalizzate

Scopo di questo studio \ue8 la valutazione degli effetti di un trattamento con onde d\u2019urto defocalizzate sull\u2019attivit\ue0 del muscolo scheletrico in termini di resistenza e di performance. Sono stati reclutati 60 soggetti sani, 30 maschi e 30 femmine. 40 pazienti sono stati sottoposti al protocollo di intervento, mentre 20 hanno partecipato al gruppo di controllo, senza ricevere il trattamento con onde d\u2019urto. Al termine di un ciclo di quattro sedute di onde d\u2019urto si \ue8 osservato un aumento dell\u2019Endurance Time e una diminuzione della Frequenza Cardiaca Massimale durante il test da sforzo a carico costante su cicloergometro. A 12 settimane dalla fine del trattamento i valori della Frequenza cardiaca Massimale non hanno subito variazioni statisticamente significative, mentre quelli dell\u2019Endurance Time hanno subito un ritorno ai valori basali. Per quanto riguarda la performance muscolare si \ue8 visto un miglioramento significativo alla valutazione T1, subito dopo la terapia con onde d\u2019urto, e alla valutazione T2, 12 settimane dopo l\u2019ultima seduta di onde d\u2019urto, rispetto alla valutazione iniziale a T0. Non \ue8 stata evidenziata una differenza statisticamente significativa tra i valori rilevati a T1e quelli a T2. I risultati di questo studio suggeriscono che il trattamento con onde d\u2019urto defocalizzate pu\uf2 portare a un miglioramento dell\u2019attivit\ue0 del muscolo scheletrico in termini di performance e di resistenza muscolare senza provocare alcun tipo di danno ai tessuti. Questi risultati aprono possibilit\ue0 di applicazione di questa metodica sia in ambito clinico (per esempio per il recupero funzionale dell\u2019amiotrofia ex non usu), sia in ambito sportivo

Improved measurement results for the Avogadro constant using a 28Si-enriched crystal

New results are reported from an ongoing international research effort to accurately determine the Avogadro constant by counting the atoms in an isotopically enriched silicon crystal. The surfaces of two 28Si-enriched spheres were decontaminated and reworked in order to produce an outer surface without metal contamination and improved sphericity. New measurements were then made on these two reconditioned spheres using improved methods and apparatuses. When combined with other recently refined parameter measurements, the Avogadro constant derived from these new results has a value of $N_A = 6.022 140 76(12) \times 10^{23}$ mol$^{-1}$. The X-ray crystal density method has thus achieved the target relative standard uncertainty of $2.0 \times 10^{-8}$ necessary for the realization of the definition of the new kilogram.Comment: postprint, 22 page, 3 figures, 14 table

Vascular risk factors in glaucoma: the results of a national survey

Background The role of vascular risk factors in glaucoma is still being debated. To assess the importance of vascular risk factors in patients with primary open-angle glaucoma (POAG), data from the medical history of 2,879 POAG patients and 973 age-matched controls were collected and analyzed. Methods Design: observational survey. Setting: 35 Italian academic centers. Study population: POAG patients and age-matched controls. In order to reduce bias consecutive patients were included. Observation procedures: data concerning vascular risk factors were collected for all patients with a detailed questionnaire. A complete ophthalmological examination with assessment of intraocular pressure (IOP), visual field, optic disc, and systemic blood pressure was performed. Main outcome measures: the ESH-ESC (European Society of Hypertension-European Society of Cardiology) guidelines were used to calculate the level of cardiovascular risk. Crude and adjusted estimates of the odds ratios (OR) were calculated for all cardiovascular risk factors in POAG and controls. Results The study included 2,879 POAG patients and 973 controls. POAG cases had a significantly higher systolic and diastolic blood pressure (p=0.001) and systolic perfusion pressure (p=0.02) as compared with controls. Also mean IOP was significantly higher in the POAG group (p=0.01), while diastolic perfusion pressure was not significantly different in the two groups. Myopia was more prevalent in the POAG group (23 vs 18%, p=0.005) as well as a positive family history for glaucoma (26 vs 12%, p= 0.004). POAG patients tended to have a higher cardiovascular risk than controls: 63% of glaucoma cases vs 55% of controls (OR: 1.38, p=0.005) had a “high” or “very high” cardiovascular risk. Conclusions The level of cardiovascular risk was significantly higher in glaucoma patients than in controls

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy : The VISIONARY Study

Funding Information: Funding was provided by Santen SA for the study, medical writing services and Rapid Service Fees. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. The contribution of IRCCS Fondazione Bietti to this work was supported by the Italian Ministry of Health and by Fondazione Roma. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Introduction: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. Methods: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored. Results: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p < 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p < 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p < 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p < 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. Conclusion: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.publishersversionPeer reviewe