Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often ...originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness. The clinical management of ATC requires a multidisciplinary approach; according to recent American Thyroid Association guidelines, surgery, radiotherapy and/or chemotherapy should be considered. In addition to conventional therapies, novel molecular targeted therapies are the most promising emerging treatment modalities. These drugs are often multiple receptor tyrosine kinase inhibitors, several of which have been tested in clinical trials with encouraging results so far. Accordingly, clinical trials are ongoing to evaluate the safety, efficacy and effectiveness of these new agents. This Review describes the updated clinical and pathological features of ATC and provides insight into the molecular biology of this disease. The most recent literature regarding conventional, newly available and future therapies for ATC is also discussed.
•Role of the roof inclination and azimuth (orientation) during the cooling period in Italy and Greece.•Lightweight and heavyweight roofs, equipped or devoid of an insulation material.•Proposal of a ...dynamic model for all the roof thermal exchanges with the indoor and outdoor environment.•Outdoor and indoor surface temperature analysis in relation to the UHI effect and cooling load.•External and internal surface temperature reduced, respectively, by 12.5 °C and 4.7 °C in the optimal configuration.
Outdoor and indoor thermal comfort in the built environment is a crucial factor impacting urban heat island (UHI), building energy consumption and occupant welfare. Building roofs are directly connected to these phenomena since high overheating on both surfaces can affect negatively all these aspects. Several innovative technologies, such as phase change material, green and cool roofs and so on, were proposed and investigated to address these environmental targets. However, an accurate design of traditional roofs is required to limit the use of these technically complex and expensive technologies.
The main objective of this work is to study the role of the inclination and azimuth (orientation) of lightweight and heavyweight roofs, equipped or devoid of an insulation material during the cooling period in Italy and Greece. The investigation was carried out by means of a dynamic model in a steady periodic regime proposed by the authors that accurately takes into account all the building roof heat exchanges. The surface temperature fluctuations, in terms of amplitude and maximum peak, were employed to find the optimal configurations to mitigate the UHI effect and cooling load. In addition, the temperature decrement factor and time lag were used to summarise the overall roof thermal behaviour. The results showed that an accurate roof design leads to a reduction of the amplitude and maximum peak of the temperature on the external surface of 12.5 °C and on the internal surface of 4.7 °C. Instead, the decrement factor varies also of 29.9 % and the time lag of 7 h.
Mechanochemistry has become a sustainable and attractive cost-effective synthetic technique, largely used within the frame of crystal engineering. Cocrystals, namely, crystalline compounds made of ...different chemical entities within the same crystal structure, are typically synthesized in bulk via mechanochemistry; however, whereas the macroscopic aspects of grinding are becoming clear, the fundamental principles that underlie mechanochemical cocrystallization at the microscopic level remain poorly understood. Time-resolved in situ (TRIS) monitoring approaches have opened the door to exceptional detail regarding mechanochemical reactions. We here report a clear example of cocrystallization between two solid coformers that proceeds through the formation of a metastable low melting binary eutectic phase. The overall cocrystallization process has been monitored by time-resolved in situ (TRIS) synchrotron X-ray powder diffraction with a customized ball milling setup, currently available at μSpot beamline at BESSY-II, Helmholtz-Zentrum Berlin. The binary system and the low melting eutectic phase were further characterized via DSC, HSM, and VT-XRPD.
The crystalline sponge method (CSM) is primarily used for structural determination by single‐crystal X‐ray diffraction of a single analyte encapsulated inside a porous MOF. As the host–guest systems ...often show severe disorder, reliable crystallographic determination is demanding; thus the dynamics of the guest entering and the formation of nanoconfined molecular aggregates has not been in the spotlight. Now, the concept is investigated of the CSM for monitoring the structural evolution of nanoconfined supramolecular aggregates of eugenol guests with displacement of DMF inside the cavities of the flexible MOF, PUM168. The interpretation of the electron density provides a series of unique detailed snapshots depicting the supramolecular guest aggregation, thus showing the tight interplay between the host flexible skeleton and the molecular guests through the DMF‐to‐eugenol exchange process.
Solvent‐to‐guest exchange and sliding nets trigger eugenol nanoaggregate formation inside the pores of a flexible pillared metal–organic framework. A detailed description of the different steps of guest aggregation in the nanoconfined environment is furnished by a series of unique crystallographic snapshots.
Ionic mass transport including electrolyte diffusivity and conductivity depends on the geometric tortuosity of the electrode. This paper compares two experimental methods that determine tortuosity ...based on diffusivity or conductivity. The polarization-interrupt method previously developed by our group determines tortuosity in terms of effective diffusivity. The blocking-electrolyte method proposed by Gasteiger and coworkers determines tortuosity in terms of effective ionic conductivity and is analyzed using a generalized transmission-line model to account for multiple sources of impedance. Tortuosity of several commercial-quality electrodes was measured using both methods, producing reasonable agreement between the two methods in most cases. The advantages and disadvantages of each method and variables that can affect the accuracy of the measurement, such as electrode wetting and model fitting, are discussed. For particular electrodes, one method may be advantageous or more conveniently applied than the other.
It is generally believed, especially among athletes and practicing sports people that the use of performanceenhancing drugs, besides improving performance, leads to the obtainment of easy results ...accompanied by glory and money gain. Unfortunately, the misuse and abuse of pharmacologically active substances have become so widespread in present day sports that the safety, the health and the longevity of far too many athletes are now compromised. More recently, athletes began the use pharmacological practices by assuming a stimulant of popular diffusion called strychnine. With the years gone by and the pharmacological progress, the use of drugs by athletes became more intense reaching a point of international phenomenon known as "doping". The restless evolution and multiplication of doping methods and substances, the fear by athletes of harsh sports and legal sanctions as well as the inadequacy of the identification techniques for illegal substances, contribute to make a not accurate evaluation of the prevalence of the Doping phenomenon. In the course of the time, the results obtained in genetics have been used in the field of sport, creating a new form of doping, called "gene doping". The athletes may be able to use gene therapy to re-engineer their bodies for better performances. One of the primary reasons for having a list of prohibited substances and methods is to protect athlete health. However, the International Olympic Committee (IOC) prohibited drugs, as beta2 agonists or glucocorticosteroids and some athletes with genuine medical conditions, were denied legitimate medical therapy. The use of drugs that have the potential to improve physical performance is restricted by anti-doping regulation. Therefore, act 376/2000 establishes three distinct types of doping offenses.Original Abstract: Opcenito se vjeruje, posebno medu sportasima i trenira sportase da uporaba lijekova za poboljsavanje izvedbe, osim poboljsanja performansi, dovodi do lakih rezultata pracenih slavom i novcanom dobiti. Nazalost, zloupotreba farmakoloski aktivnih tvari postala je tako siroko rasprostranjena u danasnjim sportovima da su sigurnost, zdravlje i dugovjecnost daleko previse sportasa sada ugrozeni. U novije vrijeme, sportasi su poceli koristiti farmakolosku praksu pretpostavljajuci stimulans popularne difuzije, koji se zove strihnin. S godinama uporaba lijekova od sportasa postala je intenzivnija i dostigla tocku medunarodnog fenomena poznatog kao "doping". Nemirna evolucija i umnazanje metoda dopinga i supstancija, strah sportasa od grubih sportova i zakonskih sankcija, kao i neadekvatnosti tehnika identifikacije za ilegalne supstance, doprinijeli su da se ne zna tocna procjenu prevalencije u doping fenomenu. Tijekom tog vremena, rezultati su dobiveni u genetici u podrucju sporta, stvarajuci novi oblik dopinga, pod nazivom "gen doping". Sportasi mogu biti u mogucnosti koristiti gensku terapiju te mijenjati svoja tijela za bolje nastupe. Jedan od glavnih razloga za popis zabranjenih tvari i metoda je da se zastiti sportasevo zdravlje. Medutim, Medunarodni olimpijski odbor (MOO) je zabranio lijekove poput je beta2-agonist ili glukokortikoidim i nekim sportasa s pravim medicinskim stanjima odbijena je legitimna medicinska terapija. Koristenje lijekova koji imaju potencijal za poboljsanje fizicke performanse ogranicena je regulacija anti-dopinga. Dakle, cin 376/2000 uspostavlja tri razlicite vrste dopinga.
The first reports of a link between thiamine and diabetes date back to the 1940s. Some years later, a role for thiamine deficiency in diabetic neuropathy became evident, and some pilot studies ...evaluated the putative effects of thiamine supplementation. However, the administration of thiamine and its lipophilic derivative benfotiamine for the treatment of this complication gained consensus only at the end of the ‘90 s. The first evidence of the beneficial effects of thiamine on microvascular cells involved in diabetic complications dates to 1996: from then on, several papers based on
in vitro
and animal models have addressed the potential use of this vitamin in counteracting diabetic microangiopathy. A few pilot studies in humans reported beneficial effects of thiamine administration on diabetic nephropathy, but, despite all promising proofs-of-concept, the possible role of thiamine in counteracting development or progression of retinopathy has not been addressed until now. Thiamine is a water-soluble vitamin, rapidly expelled from the body, with no issues of over-dosage or accumulation; unfortunately, it is non-patentable, and neither industry nor independent donors are interested in investing in large-scale randomized controlled clinical trials to investigate its potential in diabetes and its complications. Consequently, science will not be able to disprove a promising hypothesis and, more importantly, diabetic people remain deprived of a possible way to ameliorate their condition.
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