Molecular mechanisms of photosensitization induced by drugs XIV: Two different behaviours in the photochemistry and photosensitization of antibacterials containing a fluoroquinolone like chromophore

This paper deals with the photosensitizing activity of FLQs towards two different biosubstrates, membrane and DNA. Thein vitrophototoxic activity of these drugsvs.DNA presents peculiar features with respect to thatvs.membranes, probably due to a specific binding of the drugs to the double helix and to the operativeness of different photosensitization mechanisms with the two types of biosubstrates. A description of the UVA photochemistry and the photosensitizing properties of two significant examples in the FLQ family is reported. The investigated compounds are Enoxacin, 1-ethyl-6-fluoro-1,4-dihydro-4- oxo-7-[1-piperazinyl]-1,8-naphtyridine-3-carboxilic acid and Rufloxacin, 9-fluoro-2,3-dihydro-10-4´-methyl- 1´-piperazinyl-7-oxo-7H-pyrido[1,2,3−de]-1,4-benzothiazine-6-carboxylic acid

Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

Spinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38

Transient absorption study on Red Vermilion darkening in presence of chlorine ions and after UV exposure

The application of no destructive techniques in the field of Cultural Heritage is becoming fundamental to understanding degradation phenomena. In this study, Transient Absorption (TA) spectroscopy was exploited to explain the process which causes the darkening of Red Vermilion, a famous pigment known also as cinnabar. The optical properties involved in the process are studied in pure HgS and chlorine doped HgS samples, before and after exposure to UV light (365 nm). The study was carried out with particular attention on the ground state bleaching signals, directly connected to the formation of intra-gap trap levels responsible for the pigment degradation. First derivative reflectance spectra reveal the presence of these defectivities, while the analysis of Tauc plots from Kubelka Munk function confirms the reduction of energy band gap due to UV exposure. With the help of Density Functional calculations, we simulated the role of S vacancies in producing a defective alpha-phase, the consequent reduction of the energy band gap and, finally, the progressive phase transformation to the cubic metacinnabar. Transient Absorption turns out to be an important tool of diagnosis about the conservation state of pigments applied in the field of Cultural Heritage

Time through colors: A kinetic model of red vermilion darkening from Raman spectra

Darkening of Red Vermilion (cinnabar) is a well-known phenomenon which needs, at the moment, a full comprehension of its nature. Some paintings reveal a disfiguring process of blackening degradation of Red Vermilion, albeit other relics preserve the original color during the time. The presence of halide elements like Cl− ions, in addition to the light exposure, represents the most alleged cause to explain the darkening phenomenon. However, the real effect of chlorine impurities is still not completely understood. In this study, starting from a multi-technique characterization, we propose a kinetic model of mutual composition of alpha/beta cinnabar derived by the experimental darkening of pure alpha synthetic cinnabar intentionally doped with Cl− ions and treated under prolonged UV light exposure. The model was further applied to ancient samples by analyzing the Raman spectra of antique cinnabar pigments belonging to manuscripts of XIII-XVII centuries

MBSE Certification-Driven Design of a UAV MALE Configuration in the AGILE 4.0 Design Environment

This paper presents a certification-driven design process for an Unmanned Medium-Altitude- Long-Endurance (UAV MALE) air vehicle, including on-board system design and placements, electro-magnetic compatibility analysis, and thermal risk assessments. In literature, the preliminary aircraft design phase is mainly driven by mission performances and structural integrity aspects. However, the inclusion of other disciplines, like on-board system design or electro-magnetic compatibility, or thermal analysis, can lead to more efficient and cost- effective solutions and becomes paramount for non-conventional configurations like unmanned vehicles or highly electrified platforms. In the EC-funded AGILE 4.0 project (2019-2022), the traditional scope of the preliminary aircraft design is extended by including domains that are usually considered only in later design phases, such as certification, production and maintenance. In this paper, the AGILE 4.0 design environment supports the definition and execution of a certification-driven design process of a UAV MALE configuration, using a Model-Based Systems Engineering (MBSE) approach

Exports and Productivity: Comparable Evidence for 14 Countries

We use comparable micro level panel data for 14 countries and a set of identically specified empirical models to investigate the relationship between exports and productivity. Our overall results are in line with the big picture that is by now familiar from the literature: Exporters are more productive than non-exporters when observed and unobserved heterogeneity are controlled for, and these exporter productivity premia tend to increase with the share of exports in total sales; there is strong evidence in favour of self-selection of more productive firms into export markets, but nearly no evidence in favour of the learning-by-exporting hypothesis. We document that the exporter premia differ considerably across countries in identically specified empirical models. In a meta-analysis of our results we find that countries that are more open and have more effective government report higher productivity premia. However, the level of development per se does not appear to be an explanation for the observed cross-country differences.exports; productivity; micro data; international comparison

Sam68 splicing regulation contributes to motor unit establishment in the postnatal skeletal muscle

RNA-binding proteins orchestrate the composite life of RNA molecules and impact most physiological processes, thus underlying complex phenotypes. The RNA-binding protein Sam68 regulates differentiation processes by modulating splicing, polyadenylation, and stability of select transcripts. Herein, we found that Sam68-/- mice display altered regulation of alternative splicing in the spinal cord of key target genes involved in synaptic functions. Analysis of the motor units revealed that Sam68 ablation impairs the establishment of neuromuscular junctions and causes progressive loss of motor neurons in the spinal cord. Importantly, alterations of neuromuscular junction morphology and properties in Sam68-/- mice correlate with defects in muscle and motor unit integrity. Sam68-/- muscles display defects in postnatal development, with manifest signs of atrophy. Furthermore, fast-twitch muscles in Sam68-/- mice show structural features typical of slow-twitch muscles, suggesting alterations in the metabolic and functional properties of myofibers. Collectively, our data identify a key role for Sam68 in muscle development and suggest that proper establishment of motor units requires timely expression of synaptic splice variants

Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

<p>Abstract</p> <p>Background</p> <p>Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent.</p> <p>Discussion</p> <p>Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery.</p> <p>Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome.</p> <p>Summary</p> <p>Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients.</p