Management of cutaneous discomfort in patients with scleroderma: a clinical trial.

Systemic sclerosis (scleroderma) is a disease of unknown cause, the hallmark of which is induration of the skin. This bad condition of the skin influences negatively the quality of life of patients with scleroderma. The aim of the study was to verify the efficacy of two formulations, specifically designed to wash, moisturize and soothe the scleroderma skin. An independent, randomized, double blind, controlled trial was conducted in the Department of Rheumatology of "A. Galateo" Hospital in San Cesario di Lecce. Forty-six women affected by scleroderma, and treated with Iloprost every month, were divided into two groups: group 1 followed a specific treatment with cleansing formulation only, group 2 followed a combined treatment with the cleansing solution and the moisturizing solution. In addition, a third group was evaluated: 14 women, who did not undergo intravenous Iloprost therapy, were treated simultaneously with the cleansing formulation and the moisturizing formulation. The three treatments lasted for 4 weeks. Reduction in trans epidermal water loss (TEWL), increase in moisturization of the stratum corneum, reduction in Skin Score and improvement in quality of life were assessed. Very significant improvement in quality of life occurred in each group. Group 2 obtained very significant improvement in hydration and reduction in skin score and TEWL. The study showed that the daily use of both formulations proved to be effective in washing, hydrating and soothing the skin of patients with scleroderma, especially in association with Iloprost therapy

An earth pole-sitter using hybrid propulsion

In this paper we investigate optimal pole-sitter orbits using hybrid solar sail and solar electric propulsion (SEP). A pole-sitter is a spacecraft that is constantly above one of the Earth's poles, by means of a continuous thrust. Optimal orbits, that minimize propellant mass consumption, are found both through a shape-based approach, and solving an optimal control problem, using a direct method based on pseudo-spectral techniques. Both the pure SEP case and the hybrid case are investigated and compared. It is found that the hybrid spacecraft allows consistent savings on propellant mass fraction. Finally, is it shown that for sufficiently long missions (more than 8 years), a hybrid spacecraft, based on mid-term technology, enables a consistent reduction in the launch mass for a given payload, with respect to a pure SEP spacecraft

Definition of a Protocol for the Experimental Monitoring of Rising Damp in Three Different Masonry Models with Tuff, Carparo, and Lecce Stone

This work presents a new protocol for monitoring rising damp, which is applied to three masonry models made of tuff, carparo, and Lecce stone. First, the physical characteristics of each stone were derived in the laboratory, which included porosity, imbibition, drying index, permeability, capillarity, and sorptivity. In this case, the protocol provided three columns, one for each material, consisting of five blocks. A layer of cotton tissue was interposed between columned blocks to simulate the hygroscopic behavior of a mortar, allowing a quick disassembly and reassembly of the multiblock columns for a quick weighing. The bottoms of the columns were immersed in water to a level of about three centimeters, providing a constant replenishment for the phenomena of evaporation and rising in the stone. The maximum height achieved by the rising damp depends on the characteristics of the building materials, i.e., the amount and size of pores, pore connectivity, etc. Since these materials have different physical characteristics, the objective was to quantify the rising moisture level of the three materials tested, block by block, in a controlled indoor microclimate environment. The three columns were periodically weighed, the quantity of collected water was evaluated, and a thermographic survey was performed. The results show that at the end of the test, the highest level of rising damp is reached by tuff with a height of 43 cm, followed by Lecce stone and carparo with a height of 40 cm and 21 cm, respectively. The innovation of this study is the proposal of a new flexible and easy‐to‐apply method for monitoring this phenomenon. It gives clear and numerically comparable results. Moreover, it is applicable to any type of stone, allowing the user to evaluate both the existing state and different design solutions

Effects of genotype and environmental conditions on grapevine (Vitis vinifera L.) shoot morphology

Grapevine shoot morphology is widely studied for both ampelography and growing adaptation to environmental stresses. However, few is known concerning the relative contribution and interactions of the genotype and of the growing conditions to the vegetative growth. In this work, seven grapevine cultivars were studied in three geographically distant ampelographic collections to maximize the genotype and environment differences among samples. Phytomers were studied concerning the leaf area and the stem and petiole diameters and lengths. These measurements allowed the calculation of derivative parameters to describe the proportions among elements. Despite most of the studied parameters significantly discriminated both factors (cultivar and growing conditions), it was possible to identify, for each one of them, the most promising parameters based on their relative variance explanation. In fact, a negative correlation was observed between the roles of genotype and environment among the studied parameters. The low interaction effect suggested a stability in the plant behaviors, confirming the possibility to use vegetative descriptions for both cultivar discrimination and growing conditions. Future studies will be performed to develop specific indexes based on the phenotypical variability of shoot morphology described here

Wiggle-Match dating of wooden samples from iron age sites in Northern Italy

Archaeological excavations carried out at the sites of Laion/Lajen (Bolzano/Bozen) and Stufles-Oberegger (Bressanone/Brixen) in northern Italy uncovered well-preserved wooden samples in cultural layers archaeologically dated to the Iron Age. From the 2 sites, different wooden samples were recovered that were well preserved enough to allow clear identification of the tree species and of the ring structure. Among the different wooden samples, 2 were selected for radiocarbon analyses: from Laion/Lajen, a beam with an unbroken sequence of 158 rings; from Stufles-Oberegger, a combusted trunk with a sequence of 217 rings. Both samples were identified as Larix decidua species. From each sequence, single rings were selected and submitted for accelerator mass spectrometry (AMS) 14C dating analysis at CEDAD. Conventional 14C ages were then calibrated to calendar ages using the IntCal04 atmospheric data set, while the statistical constraints resulting from the defined ring sequence were used to develop a wiggle-matching approach by making use of the Bayesian analysis functions available in OxCal. The obtained results are an important contribution in refining the chronology of the studied sites

Nedd4-2 haploinsufficiency causes hyperactivity and increased sensitivity to inflammatory stimuli

Nedd4-2 (NEDD4L in humans) is a ubiquitin protein ligase best known for its role in regulating ion channel internalization and turnover. Nedd4-2 deletion in mice causes perinatal lethality associated with increased epithelial sodium channel (ENaC) expression in lung and kidney. Abundant data suggest that Nedd4-2 plays a role in neuronal functions and may be linked to epilepsy and dyslexia in humans. We used a mouse model of Nedd4-2 haploinsufficiency to investigate whether an alteration in Nedd4-2 levels of expression affects general nervous system functions. We found that Nedd4-2 heterozygous mice are hyperactive, have increased basal synaptic transmission and have enhanced sensitivity to inflammatory pain. Thus, Nedd4-2 heterozygous mice provide a new genetic model to study inflammatory pain. These data also suggest that in human, SNPs affecting NEDD4L levels may be involved in the development of neuropsychological deficits and peripheral neuropathies and may help unveil the genetic basis of comorbidities

Respicelltm: An innovative dissolution apparatus for inhaled products

To overcome some of the shortfalls of the types of dissolution testing currently used for pulmonary products, a new custom-built dissolution apparatus has been developed. For inhalation products, the main in vitro characterisation required by pharmacopoeias is the deposition of the active pharmaceutical ingredient in an impactor to estimate the dose delivered to the target site, i.e., the lung. Hence, the collection of the respirable dose (<5 µm) also appears to be an essential requirement for the study of the dissolution rate of particles, because it results as being a relevant parameter for the pharmacological action of the powder. In this sense, dissolution studies could become a complementary test to the routine testing of inhaled formulation delivered dose and aerodynamic performance, providing a set of data significant for product quality, efficacy and/or equivalence. In order to achieve the above-mentioned objectives, an innovative dissolution apparatus (RespiCell™) suitable for the dissolution of the respirable fraction of API deposited on the filter of a fast screening impactor (FSI) (but also of the entire formulation if desirable) was designed at the University of Parma and tested. The purpose of the present work was to use the RespiCell dissolution apparatus to compare and discriminate the dissolution behaviour after aerosolisation of various APIs characterised by different physico-chemical properties (hydrophilic/lipophilic) and formulation strategies (excipients, mixing technology)

Porcine sclera as a model of human sclera for in vitro transport experiments: histology, SEM, and comparative permeability

PURPOSE: To evaluate porcine sclera as a model of human sclera for in vitro studies of transscleral drug delivery of both low and high molecular weight compounds. METHODS: Human and porcine scleras were characterized for thickness and water content. The tissue surface was examined by scanning electron microscopy (SEM), and the histology was studied with hematoxylin-eosin staining. Comparative permeation experiments were performed using three model molecules, acetaminophen as the model compound for small molecules; a linear dextran with a molecular weight of 120 kDa as the model compound for high molecular weight drugs; and insulin, which was chosen as the model protein. Permeation parameters such as flux, lag time, and permeability coefficient were determined and compared. RESULTS: Human and porcine scleras have a similar histology and collagen bundle organization. The water content is approx 70% for both tissues while a statistically significant difference was found for the thickness, porcine sclera being approximately twofold thicker than human sclera. Differences in thickness produced differences in the permeability coefficient. In fact, human sclera was found to be two to threefold more permeable toward the three molecules studied than porcine sclera. CONCLUSIONS: The results obtained in the present paper prove that porcine sclera can be considered a good model for human sclera for in vitro permeation experiments of both low and high molecular weight compounds. In fact, if the different tissue thickness is taken into account, comparable permeability was demonstrated. This suggests a possible use of this model in the evaluation of the transscleral permeation of new biotech compounds, which currently represent the most innovative and efficient therapeutic options for the treatment of ocular diseases

Investigation on the composition of agarose–collagen i blended hydrogels as matrices for the growth of spheroids from breast cancer cell lines

Three-dimensional (3D) cell culture systems mimic the structural complexity of the tissue microenvironment and are gaining increasing importance as they resemble the extracellular matrix (ECM)–cell and cell–cell physical interactions occurring in vivo. Several scaffold-based culture systems have been already proposed as valuable tools for large-scale production of spheroids, but they often suffer of poor reproducibility or high costs of production. In this work, we present a reliable 3D culture system based on collagen I-blended agarose hydrogels and show how the variation in the agarose percentage affects the physical and mechanical properties of the resulting hydrogel. The influence of the different physical and mechanical properties of the blended hydrogels on the growth, size, morphology, and cell motility of the spheroids obtained by culturing three different breast cancer cell lines (MCF-7, MDA-MB-361, and MDA-MB-231) was also evaluated. As proof of concept, the cisplatin penetration and its cytotoxic effect on the tumor spheroids as function of the hydrogel stiffness were also investigated. Noteworthily, the possibility to recover the spheroids from the hydrogels for further processing and other biological studies has been considered. This feature, in addition to the ease of preparation, the lack of cross-linking chemistry and the high re-producibility, makes this hydrogel a reliable biomimetic matrix for the growth of 3D cell structures