From ancient leech to direct thrombin inhibitors and beyond: New from old

Medicinal leeches have been used in health care since before written history, with widely varying popularity over the centuries. Nowadays, medicinal leech therapy is mainly used in plastic and reconstructive microsurgery, with new interesting potential therapeutic applications in many other diseases. The leech's best-known salivary product, hirudin — one of the most powerful natural anticoagulants — was the only remedy to prevent blood clotting until the discovery of heparin. Starting from hirudin, pharmacological research succeeded in developing new anticoagulants, which represent a cornerstone of prevention and treatment of thromboembolic disease. While we are perhaps on the threshold of a new era of anticoagulation, with the development of FXI and XII inhibitors and direct reversible covalent thrombin inhibitors, which promise to achieve effective anticoagulation without bleeding risk. This review retraces the intriguing journey of these drugs in cardiovascular disease, highlighting the fil rouge that links the ancient leech to the current and oncoming antithrombotic therapy. We think that knowledge of the past is key to understanding and appreciating the present and to seize future opportunities

The record of the Paleocene-Eocene thermal maximum in the Ager Basin (Central Pyrenees, Spain)

The sedimentary record straddling the Paleocene/Eocene boundary in the Ager Basin (southern Central Pyrenees) was investigated by combining facies analysis, sequence stratigraphy and stable isotope data, within an interval characterized by a great variability of depositional environments. The occurrence of the Paleocene-Eocene Thermal Maximum (PETM) climatic anomaly is tentatively constrained by analogy with its stratigraphic range in the adjacent Tremp-Graus Basin. The main body of the carbon isotope excursion associated with the PETM may be recorded by lacustrine carbonates characterized by a ~ -3‰ shift in d13C with respect to analogous deposits of Thanetian age; a similar shift is recorded between in situ and resedimented pedogenic carbonates, a feature that suggests the partial erosion of the P/E boundary in the Ager Basin

Affective interdependence and welfare

Purely affective interaction allows the welfare of an individual to depend on her own actions and on the profile of welfare levels of others. Under an assumption on the structure of mutual affection that we interpret as “non-explosive mutual affection,” we show that equilibria of simultaneous-move affective interaction are Pareto optimal independently of whether or not an induced standard game exists. Moreover, if purely affective interaction in-duces a standard game, then an equilibrium profile of actions is a Nash equilibrium of the game, and this Nash equilibrium and Pareto optimal profile of strategies is locally dominant

Liberal parentalism

What normative constraints should bind parents (or policy makers) if they intervene in the choices of children (or constituencies) whose preferences evolve over time? For a sophisticated child who anticipates correctly his preference change, we prove that generically there exist parental interventions that are Pareto improving over the backward induction path that the child will follow on his own. If, in contrast, the child misperceives his future preferences, Pareto improving interventions might not exist, and even nudges might be painfully sobering. The parent may then choose to minimize the maximal disappointment along time that her benevolent intervention would cause

The first 3500 years of aspirin history from its roots - A concise summary

none3Aspirin is currently the most widely used drug worldwide, and has been clearly one of the most important pharmacological achievements of the twentieth century. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back >3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome. The modern history of aspirin precursors, salicylates, began in 1763 with Reverend Stone - who first described their antipyretic effects - and continued in the 19th century with many researchers involved in their extraction and chemical synthesis. Bayer chemist Felix Hoffmann synthesized aspirin in 1897, and 70 years later the pharmacologist John Vane elucidated its mechanism of action in inhibiting prostaglandin production. Originally used as an antipyretic and anti-inflammatory drug, aspirin then became, for its antiplatelet properties, a milestone in preventing cardiovascular and cerebrovascular diseases. The aspirin story continues today with the growing evidence of its chemopreventive effect against colorectal and other types of cancer, now awaiting the results of ongoing primary prevention trials in this setting. This concise review revisits the history of aspirin with a focus on its most remote origins.Montinari, Maria Rosa; Minelli, Sergio; De Caterina, RaffaeleMontinari, Maria Rosa; Minelli, Sergio; De Caterina, Raffael

How to describe and predict plasticization in glassy polymeric membranes for gas separations

In glassy polymeric membranes, gas permeability shows different trends as upstream pressure increases, including the monotonous decline, a monotonous increase, as well as an initial decline followed by a subsequent increase after a minimum permeability value is reached. The minimum value, whenever present, occurs at a pressure conventionally indicated as the plasticization pressure. It is currently accepted that permeability behavior can be conveniently well described by a transport model only below plasticization pressure, while above that value the onset of additional phenomena at higher pressures are responsible of the observed increase in permeability and decrease in selectivity. On the other hand, the plasticization phenomenon has not been further inspected thus far, in terms of material property variations. With the aim to reach to a deeper understanding of the phenomenon, we have experimentally inspected the behavior of Matrimid polyimide membranes, by analyzing both transport and mechanical properties. The permeability behavior and the “plasticization” effects induced by CO2 have been studied by increasing the upstream pressure at different fixed values of downstream pressure. The mechanical properties studied include elastic modulus and viscoelastic response of samples saturated at different CO2 pressures up to and above plasticization pressure. The trends obtained are rather interesting and actually not fully in line with what expected based on the current qualitative interpretation. We also show that the observed gas permeability behavior can be described by considering only a solution-diffusion model in which the penetrant mobility varies with its concentration in the polymer matrix through an exponential law, with two adjustable parameters only. Diffusivity is thus taken as the product of molecular mobility and a thermodynamic factor, calculated by using the NELF model for thermodynamic properties of the glassy phase. It is observed that by fitting the only two adjustable parameters to the initial branch of the permeability isotherm, the above solubility diffusivity model allows the prediction of the plasticization pressure, at all values of downstream pressures used, without introducing any additional physical phenomenon. The agreement observed between model calculations and experimental data of CO2 permeability in Matrimid, as well as in various glassy polymers, is very satisfactory. That allows us to offer a deeper insight on the so-called plasticization phenomenon. The analysis of the permeability and the solubility isotherms, and the evaluation of concentration and swelling profiles in the membrane, show that in some cases the plasticization phenomena take place after part of the membrane has turned into rubbery phase. However, in other relevant cases as in Matrimid, the minimum in permeability is observed when the entire membrane is still glassy (and characterized by mechanical behavior comparable to the pure “dry” material), but with a polymer swelling sufficient for a permeability increase. Finally, it is observed that all parameters used have a defined independent physical meaning, which might lead to the development of general correlations with both polymer and penetrant properties, based on which permeability predictions can be obtained

New Perspectives on Catalytic Hydrogen Production by the Reforming, Partial Oxidation and Decomposition of Methane and Biogas

The article provides a short review on catalyst-based processes for the production of hydrogen starting from methane, both of fossil origin and from sustainable processes. The three main paths of steam- and dry-reforming, partial oxidation and thermo-catalytic decomposition are briefly introduced and compared, above all with reference to the latest publications available and to new catalysts which obey the criteria of lower environmental impact and minimize the content of critical raw materials. The novel strategies based on chemical looping with CO2 utilization, membrane separation, electrical-assisted (plasma and microwave) processes, multistage reactors and catalyst patterning are also illustrated as the most promising perspective for CH4 reforming, especially on small and medium scale. Although these strategies should only be considered at a limited level of technological readiness, research on these topics, including catalyst development and process optimization, represents the crucial challenge for the scientific community

Reply to the comment A.J. Kassman and D.B. Losee on the "Effect of gallium ions and of preparation methods on the structural properties of cobalt-molybdenum-alumina catalysts"

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