Efficient computation of hashes

The sequential computation of hashes at the core of many distributed storage systems and found, for example, in grid services can hinder efficiency in service quality and even pose security challenges that can only be addressed by the use of parallel hash tree modes. The main contributions of this paper are, first, the identification of several efficiency and security challenges posed by the use of sequential hash computation based on the Merkle-Damgard engine. In addition, alternatives for the parallel computation of hash trees are discussed, and a prototype for a new parallel implementation of the Keccak function, the SHA-3 winner, is introduced

Spray congealing: An emerging technology to prepare solid dispersions with enhanced oral bioavailability of poorly water soluble drugs

The low and variable oral bioavailability of poorly water soluble drugs remains a major concern for the pharmaceutical industry. Spray congealing is an emerging technology for the production of solid dispersion to enhance the bioavailability of poorly soluble drugs by using low-melting hydrophilic excipients. The main advantages are the absence of solvents and the possibility to obtain spherical free-flowing microparticles (MPs) by a relatively inexpensive, simple, and one-step process. This review aims to fully describe the composition, structure, physico-chemical properties, and characterization techniques of spray congealed-formulations. Moreover, the influence of these properties on the MPs performance in terms of solubility and dissolution enhancement are examined. Following, an overview of the different spray congealed systems developed to increase the oral drug bioavailability is provided, with a focus on the mechanisms underpinning the bioavailability enhancement. Finally, this work gives specific insights on the main factors to be considered for the rational formulation, manufacturing, and characterization of spray congealed solid dispersions

Tuning and Locking the Localized Surface Plasmon Resonances of CuS (Covellite) Nanocrystals by an Amorphous CuPdxS Shell

[Image: see text] We demonstrate the stabilization of the localized surface plasmon resonance (LSPR) in a semiconductor-based core–shell heterostructure made of a plasmonic CuS core embedded in an amorphous-like alloyed CuPd(x)S shell. This heterostructure is prepared by reacting the as-synthesized CuS nanocrystals (NCs) with Pd(2+) cations at room temperature in the presence of an electron donor (ascorbic acid). The reaction starts from the surface of the CuS NCs and proceeds toward the center, causing reorganization of the initial lattice and amorphization of the covellite structure. According to density functional calculations, Pd atoms are preferentially accommodated between the bilayer formed by the S–S covalent bonds, which are therefore broken, and this can be understood as the first step leading to amorphization of the particles upon insertion of the Pd(2+) ions. The position and intensity in near-infrared LSPRs can be tuned by altering the thickness of the shell and are in agreement with the theoretical optical simulation based on the Mie–Gans theory and Drude model. Compared to the starting CuS NCs, the amorphous CuPd(x)S shell in the core–shell nanoparticles makes their plasmonic response less sensitive to a harsh oxidation environment (generated, for example, by the presence of I(2))

Tailoring the release of drugs having different water solubility by hybrid polymer-lipid microparticles with a biphasic structure

The aim of this study is to investigate the potential of hybrid polymer-lipid microparticles with a biphasic structure (b-MPs) as drug delivery system. Hybrid b-MPs of Compritol & REG;888 ATO as main lipid constituent of the shell and polyethylene glycol 400 as core material were produced by an innovative solvent-free approach based on spray congealing. To assess the suitability of hybrid b-MPs to encapsulate various types of APIs, three model drugs (fluconazole, tolbutamide and nimesulide) with extremely different water solubility were loaded into the polymeric core. The hybrid systems were characterized in terms of particle size, morphology and physical state. Various techniques (e.g. optical, Confocal Raman and Scanning Electron Microscopy) were used to investigate the influence of the drugs on different aspects of the b-MPs, including external and internal morphology, properties at the lipid/polymer interface and drug distribution. Hybrid b-MPs were suitable for the encapsulation of all drugs (encapsulation efficiency > 90 %) regardless the drug hydrophobic/hydrophilic properties. Finally, the drug release behaviors from hybrid b-MPs were studied and compared with traditional solid lipid MPs (consisting of only the lipid carrier). Due to the combination of lipid and polymeric materials, hybrid b-MPs showed a wide array of release profiles that depends on their composition, the type of loaded drug, the drug loading amount and location, providing a versatile platform and allowing the formulators to finely balance the release performance of drugs intended for oral administration. Overall, the study demonstrates that hybrid, solvent-free b-MPs produced by spray congealing are an extremely versatile delivery platform able to efficiently encapsulate and release very different types of drug compounds

Grice subtalar arthrodesis of bilateral adult flatfoot in a professional dancer: A case report

Background and aim: Adult acquired flatfoot deformity (AAFD) is a common pathology and an important cause of pain and disability. This deformity causes a progressive flattening of the foot arch which has traditionally been associated with posterior tibialis tendon (PTT) dysfunction. Operative treatment is indicated after the failure of conservative management aiming to achieve proper alignment of the hindfoot and to maintain as much flexibility as possible. If subtalar osteoarthritis is present, subtalar arthrodesis is usually the best therapeutic option. Grice-Green subtalar arthrodesis is a widely used procedure. Methods: This report describes a case of bilateral painful AAFD in a 39-years old female professional dancer treated with Grice-Green subtalar arthrodesis with an autologous corticocancellous graft harvested from the ipsilateral proximal tibia. Surgeries were performed 3 years apart from each other. Results: The patient had good clinical and radiological outcomes. She returned to dance 4 months after surgery with no referred pain or limitations. Conclusions: Due to its versatility and capability to restore the shape and thickness of the hindfoot Grice-Green procedure is a simple and effective technique for the treatment of AAFD with subtalar osteoarthritis and a valid option to solve professional disabilities as it happened in this case with a professional dancer. (www.actabiomedica.it)

Glutathione-loaded solid lipid microparticles as innovative delivery system for oral antioxidant therapy

The present study aimed to develop a novel formulation containing glutathione (GSH) as an oral antioxidant therapy for the treatment of oxidative stress-related intestinal diseases. To this purpose, solid lipid microparticles (SLMs) with Dynasan 114 and a mixture of Dynasan 114 and Dynasan 118 were produced by spray congealing technology. The obtained SLMs had main particle sizes ranging from 250 to 355 µm, suitable for oral administration. GSH was efficiently loaded into the SLMs at 5% or 20% w/w and the encapsulation process did not modify its chemico-physical properties, as demonstrated by FT-IR, DSC and HSM analysis. Moreover, in vitro release studies using biorelevant media showed that Dynasan 114-based SLMs could efficiently release GSH in various intestinal fluids, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay demonstrated the good radical scavenging activity of this formulation. Dynasan 114-based SLMs exhibited an excellent biocompatibility on intestinal HT-29 cells at concentrations up to 2000 µg/mL. SLMs containing GSH alone or together with another antioxidant agent (catalase) were effective in reducing intracellular reactive oxygen species (ROS) levels. Overall, this study indicated that spray congealed SLMs are a promising oral drug delivery system for the encapsulation of one or more biological antioxidant agents for local intestinal treatment

Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences

Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed

Factors Influencing Greenways Use in Italy: Definition of a Method for Estimation

The issue of non-motorized mobility in the last decades has seen increasing attention at the international level. Also in Italy we assisted at the creation of hundreds of miles of trails dedicated to cycling and walking, many of which meet the greenway definition of the European Greenways Association: “Communication routes reserved exclusively for non-motorized journeys, developed in an integrated manner which enhances both the environment and quality of life of the surrounding area. These routes should meet satisfactory standards of width, gradient, and surface condition to ensure that they are both user-friendly and low-risk for users of all abilities. In this respect, canal towpaths and disused railway lines are a highly suitable resource for the development of greenways” (EGWA, 2002). More generally, greenways are green infrastructures that can be planned at different scales and for multiple purposes (ecological, recreational, cultural, non-motorized mobility) (Fabos, 1995; Ahern, 1995). Various methodologies and several studies on greenways planning have been conducted also in Italy (Rovelli et al., 2004; Toccolini et al., 2006; Senes et al., 2010). The growing number of infrastructures built and the related costs, combined with the recent economic crisis, led to an increasing need for public bodies to evaluate each project in terms of its ability to meet the needs of the communities, particularly in terms of attractiveness for users and benefits (not only economic) for local communities. To do this, planners and decision makers need to be provided with: 1) updated and consistent data on greenways and trails users; 2) models, based on the previous data, that can help to predict the number of users on a planned infrastructure. In such a context, the aim of this research was to assess the relationships between the number of users detected along some Italian greenways and the characteristics of the territory crossed (in terms of population and environment), in order to define a model capable of estimating the potential users of a greenway before it is realized. It represents one of the first attempts in Italy

An instrument for low-level measurements of the leakage current from high-voltage biased detectors

Resistive Plates Chambers (RPC) are detectors biased at High-Voltage (HV) in excess of 4 kV. When fired by a particle, they develop a large signal current that can be read across a small resistance, 100 Omega or so. A characterization has been made of their ageing as a function of the behaviour of their leakage current with time. An array of 10 detectors has been developed for this purpose. We present the instrument designed and built to perform a continuous and automatic monitoring of the leakage current from each detector of the array, while the system is taking data. For the particular biasing set-up adopted, the current has been measured in series to the terminal connected to the HV of every channel. Since the small value of the currents, order of tens of nA, a special circuit solution and special precautions have been adopte

NaDES as a green technological approach for the solubility improvement of BCS class II APIs: An insight into the molecular interactions

Recently, Natural Deep Eutectic Solvents (NaDES) have emerged as potential solvents for boosting drug bioavailability. In this work, the mechanism of solubility enhancement of some APIs belonging to BCS class II (tolbutamide, nimesulide, domperidone and cinnarizine) in these eutectic bio-solvents was investigated in order to get deeper insights into the molecular interactions between the NaDES components and the selected drugs. Different NaDES formulations based on choline chloride, proline, solid organic acids (citric, tartaric and malic acid), sugars (glucose and xylitol) and water were prepared by mild heating (70 °C). Characterization of unloaded NaDES (pH, Karl Fisher titration, viscosity and FTIR analysis) indicated that the type of Hydrogen Bond Acceptor (HBA) and Hydrogen Bond Donor (HBD), their molar ratio as well as water amount strongly affect the extent of H-bonding interactions. Hard gelatin capsules filled with NaDES maintained their integrity until 6 months, proving that all water molecules participate in H-bond network. APIs' solubility enhancement was significant in all NaDES with respect to buffer solutions (pH 1.2 and 6.8). Analysing NaDES having Choline as HBA, it was found that the solubility of smaller molecules increased using larger HBD, while higher molecular weight APIs can be better inserted into the network formed by smaller HBD. NOE experiments demonstrated the formation of a robust supramolecular structure among the protons of choline, those of organic acid and water. In addition, 1D ROESY spectra revealed for the first time the crucial role of choline (methyl groups) in establishing hydrophobic interactions with the relative aliphatic or aromatic portion of the drugs. These data suggest the complex structure of the API-NaDES supramolecular assembly and underline that drug solubility is dependent on a balance network of H-bonds and hydrophobic interactions as well. Understanding the type of interactions between the API and NaDES is essential for their use as effective solubilisation aid