The Gamblers' Temperament and Character Inventory (TCI) Personality Profile

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Alpine tectonic evolution and thermal water circulations of the Argentera Massif (South-Western Alps)

Three groups of thermal springs with temperatures close to 70 °c discharge both in the core (at bagni di Vinadio and terme di Valdieri) and on the external margin (at Berthemont-Les-Bains) of the Argentera Massif. Detailed structural field analysis carried out on the hydrothermal sites allows us to delineate both a model of Alpine tectonic evolution of the Argentera Massif and the patterns of hydrothermal circulation that were active during its final exhumation. the observed fault rock assemblages provide information relative to deformation that occurred in viscous, frictional-to-viscous and frictional crustal regimes. During the Early Miocene, the bersezio Fault Zone and the Fremamorta shear Zone, two main mylonitic shear zones, mainly accommodated regional transpression and provided pathways for fluid flow promoting mineral reactions in greenschist facies. During the Late Miocene-Early Pliocene, frictional-to-viscous deformation affected the massif, which underwent predominant transpression in the internal sectors and extension on the external margin. During the Plio-Pleistocene, deformation in frictional condition accompanied the final exhumation of the massif in a transpressive regime and resulted in the development of the NW-SE striking cataclastic zones. The hydraulic properties of these structures mainly influence the patterns of the active thermal circulations and the localization of the recharge and discharge zones. At Berthemont these faults represent conduits, whereas at Vinadio and Valdieri they form complex systems of conduits and barriers. In these two latter sites, the cataclastic faults compose flower structures that constrain laterally the thermal fluid flows while intensely fractured granites sited at depth constitute a highly-transmissive geothermal reservoir. Less permeable migmatitic gneisses overlaying the granites prevent a massive infiltration of the cold fluids at depth. This context favours within the high-ermeability fractures granites the development of buoyancy-driven flows which combined with topographically-driven flows, provided the conditions for the pflow of the high-temperature waters. © Birkhäuser Verlag, Basel, 2009

Alternating block copolymer-based nanoparticles as tools to modulate the loading of multiple chemotherapeutics and imaging probes

Abstract Cancer therapy often relies on the combined action of different molecules to overcome drug resistance and enhance patient outcome. Combined strategies relying on molecules with different pharmacokinetics often fail due to the lack of concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due to their ability to enhance treatment efficiency, improve drug pharmacokinetics, and reduce adverse effects, polymer nanoparticles (PNPs) have been widely investigated as co-delivery vehicles for cancer therapies. However, co-encapsulation of different drugs and probes in PNPs requires a flexible polymer platform and a tailored particle design, in which both the bulk and surface properties of the carriers are carefully controlled. In this work, we propose a core-shell PNP design based on a polyurethane (PUR) core and a phospholipid external surface. The modulation of the hydrophilic/hydrophobic balance of the PUR core enhanced the encapsulation of two chemotherapeutics with dramatically different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL) and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained unchanged among the platforms, resulting in un-modified cellular uptake and in vivo biodistribution. We demonstrate that the choice of PUR core allowed a high entrapment efficiency of all drugs, superior or comparable to previously reported results, and that higher core hydrophilicity enhances the loading efficiency of the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing the PUR core did not alter the surface properties of the carriers, since all particles showed a similar behavior in terms of cell internalization and in vivo biodistribution. We also show that PUR PNPs have high passive tumor accumulation and that they can efficient co-deliver the two drugs to the tumor, reaching an 11-fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. Statement of Significance Exploiting the synergistic action of multiple chemotherapeutics is a promising strategy to improve the outcome of cancer patients, as different agents can simultaneously engage different features of tumor cells and/or their microenvironment. Unfortunately, the choice is limited to drugs with similar pharmacokinetics that can concomitantly accumulate in tumors. To expand the spectrum of agents that can be delivered in combination, we propose a multi-compartmental core-shell nanoparticles approach, in which the core is made of biomaterials with high affinity for drugs of different physical properties. We successfully co-encapsulated Doxorubicin Hydrochloride, Docetaxel, and contrast agents and achieved a significantly higher concomitant accumulation in tumor versus free drugs, demonstrating that nanoparticles can improve synergistic cancer chemotherapy

A comprehensive overview on Kratom

Kratom (Mitragyna speciosa Korth) is a tropical tree, indigenous to South East Asia. Historically, the plant is locally used as a stimulant, a remedy in traditional medicine and in social context. Imported to Western countries, Kratom is classified as a novel psychoactive substance (NPS). A systematic review of the literature on Mitragyna speciosa and its main constituents was carried by our international multidisciplinary group. Results were qualitatively analysed in three main areas of interest: in-vitro and preclinical data on pharmacology and behavioral effects, laboratoristic techniques for identification/characterization, epidemiological/toxicological reports on humans. At present, there is no systematic data on the prevalence of Kratom use in all the native countries, but it seems to be considerable. In South-East Asia, Kratom, even if banned, might be still considered a better option than other illicit drugs, an alternative opioid treatment, a “natural” remedy with no real social stigma attached to its consumption. In parallel, this ethno-drug seems to be popular in Western countries, largely unregulated, easily available on the Internet. Kratom pharmacology appears to be complex, with many alkaloids involved. The subjective effects in humans are very peculiar and seem to be dose-dependent, ranging from psycho-stimulant to sedative-narcotic. Available data on Kratom suggest caution: this psychoactive plant could exhibit a serious harmful potential. Kratom use seems to be associated with drug dependency, development of withdrawal symptoms, craving, serious adverse effects and life-threatening effects in a multidrug-intoxicating scenario. On the other hand, its anxyiolitic, antidepressant and analgesic properties deserve to be further studied

PO-0857: GTV-based prescription and Monte Carlo treatment planning in Cyberknife treatments for lung lesions

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Recreational Drug Misuse and Its Potential Contribution to Male Fertility Levels’ Decline: A Narrative Review

Recreational drug intake may be associated with a range of medical untoward consequences, including male infertility. However, as the related evidence is still limited, the main outcome of this review is to provide a better understanding of the existence of any association between recreational drug misuse and male fertility levels’ decline. Whilst searching the MEDLINE/PubMed, a comprehensive overview of the literature regarding male infertility and substances of abuse (e.g., phytocannabinoids, opiates/opioids, stimulants, ‘herbal highs’, psychedelics, and ‘novel psychoactive substances) was here undertaken. Due to the paucity of robust, high-quality, empirical, human studies, a narrative strategy was here preferred over a systematic approach. Relevant data are qualitatively analyzed and presented in a table. Although most available evidence is in support of a detrimental role of cannabis on human spermatogenesis, a few remaining studies failed to document any effect of this drug on seminal quality, and it is not clear to which extent this drug impacts fertility rates/time to pregnancy. The current understanding of the impact of opiate-, cocaine- and amphetamine/stimulant-misuse on human reproduction is widely unknown, and most studies dealing with this matter represent only an extrapolation of data derived from specific clinical circumstances. Although the message of ‘no smoking, no alcohol and no street drugs’ should always be offered as good health advice to all patients seeking medical help for fertility issues, robust scientific clinical evidence in support of a direct detrimental impact of recreational drugs on spermatogenesis is scant to date

An integrated approach to evaluate PAH exposure

Introduction - An integrated evaluation of PAH exposure should consider different routes of absorption, reliability and specificity of biomarkers of dose, and individual susceptibility. Material and Methods - The present study investigated the exposure to PAHs in coke oven workers (n=100), asphalt pavers (n=98) and ground construction workers (n=47), by means of environmental exposure and biological monitoring. Results \u2013 Personal exposure to total airborne PAHs [from naphtalene to indeno(1,2,3-cd)pyrene] in coke oven workers (median 140 \ub5g/m3), was much higher than in pavers exposed to bitumen fumes (0.6 \ub5g/m3), or in construction workers (0.4 \ub5g/m3),. Urinary 1-hydroxypyrene (1-HOP) in end-shift samples was significantly higher in cokeoven workers (2.2 \ub5g/l) than in asphalt pavers (0.7 \ub5g/l) and in construction workers (0.4 \ub5g/l). An increasing trend in 1-HOP levels, over the workweek and the workshift was registered. A similar trend was observed for urinary 2-hydroxyfluorene (2-FLE) and 3-hydroxyphenanthrene (3-PHE) as well as for some unmetabolised PAH in urine. In smokers with low exposures an important contribution to biomarkers was given by tobacco smoking. PAH-DNA adducts in peripheral blood lymphocytes were not associated with external exposure. Genetic polymorphisms of metabolic and DNA repairing enzymes (CYP1A1, GSTM1, GSTT1, XPD) did not appear to influence the levels of biomarkers. Total dermal contamination of PAHs in pavers, assessed in a subgroup of workers (n=22), ranged from 23 to 623 \ub5g. Significant correlations between dermal phenanthrene or pyrene and 1-HOP (r = 0.41 and 0.55), suggest that dermal exposure significantly contributes to the internal dose of these compounds. Conclusion \u2013 Our results suggest that urinary biomarkers of PAHs, integrating exposure from all sources and routes, are reliable tools for risk assessment in occupational health

Exploring the Association Between Suicidal Thoughts, Self-Injury, and GLP-1 Receptor Agonists in Weight Loss Treatments: Insights from Pharmacovigilance Measures and Unmasking Analysis

© 2024 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: The study addresses concerns about potential psychiatric side effects of Glucagon-like peptide-1 receptor agonists (GLP-1 RA). Aim: The aim of this work was to analyse adverse drug reports (ADRs) from the Food and Drug Administration Adverse Events Reporting System (FAERS) using metformin and orlistat as comparators. Methods: Descriptive and pharmacovigilance disproportionality analyses was performed. Results: A total of 209,354 ADRs were reported, including 59,300 serious cases. Of those, a total of 5378 psychiatric disorder cases, including 383 ‘serious’ cases related to selected ADRs were registered during 2005–2023. After unmasking, 271 cases where individual GLP-1 RA were implicated showing liraglutide (n = 90; Reported Odds Ratio (ROR) = 1.64), exenatide (n = 67; ROR = 0.80), semaglutide (n = 61; ROR = 2.03), dulaglutide (n = 45; ROR = 0.84), tirzepatide (n = 5; ROR = 1.76) and albiglutide (n = 2; ROR = 0.04). A greater association between these ADRs with metformin was observed, but not orlistat. With regards to selected preferred terms (PTs), 42 deaths including 13 completed suicides were recorded. Suicidal ideation was recorded in n = 236 cases for 6/7 GLP-1 RA (excluding lixisenatide). Discussion: Suicide/self-injury reports pertaining to semaglutide; tirzepatide; and liraglutide were characterised, although lower than metformin. It is postulated that rapid weight loss achieved with GLP-1 RA can trigger significant emotional, biological, and psychological responses, hence possibly impacting on suicidal and self-injurious ideations. Conclusions: With the current pharmacovigilance approach, no causality link between suicidal ideation and use of any GLP-1 RA can be inferred. There is a need for further research and vigilance in GLP-1 RA prescribing, particularly in patients with co-existing psychiatric disorders.Peer reviewe