Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

Mucoadhesive budesonide formulation for the treatment of eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a chronic immune/antigen-mediated esophageal inflammatory disease for which off-label topical corticosteroids (e.g., budesonide) are widely used in clinic. In general, thickening excipients are mixed with industrial products to improve the residence time of the drug on the esophageal mucosa. The compounding procedures are empirical and the composition is not supported by real physicochemical and technological characterization. The current study aimed to propose a standardized budesonide oral formulation intended to improve the resistance time of the drug on the esophageal mucosa for EE treatment. Different placebo and drug-loaded (0.025% w/w) formulations were prepared by changing the percentage of xanthan gum alone or in ratio 1:1 with guar gum. Both excipients were added in the composition for their mucoadhesive properties. The formulative space was rationalized based on the drug physicochemical stability and the main critical quality attributes of the formulation, e.g., rheological properties, syringeability, mucoadhesiveness and in vitro penetration of budesonide in porcine esophageal tissue. The obtained results demonstrated that gums allowed a prolonged residence time. However, the concentration of the mucoadhesive polymer has to be rationalized appropriately to permit the syringeability of the formulation and, therefore, easy dosing by the patient/caregiver

The TNG Near Infrared Camera Spectrometer

NICS (acronym for Near Infrared Camera Spectrometer) is the near-infrared cooled camera-spectrometer that has been developed by the Arcetri Infrared Group at the Arcetri Astrophysical Observatory, in collaboration with the CAISMI-CNR for the TNG (the Italian National Telescope Galileo at La Palma, Canary Islands, Spain). As NICS is in its scientific commissioning phase, we report its observing capabilities in the near-infrared bands at the TNG, along with the measured performance and the limiting magnitudes. We also describe some technical details of the project, such as cryogenics, mechanics, and the system which executes data acquisition and control, along with the related software.Comment: 7 pages, 5 figures, compiled with A&A macros. A&A in pres

Poly(methyl methacrylate) salt as film forming material to design orodispersible films

This work aims to evaluate the possible use of a poly(sodium methacrylate, methyl methacrylate) (NaPMM2) plasticized by PEG400 in design orodispersible films (ODF). Placebo ODF prepared by solvent casting were intended to study the impact of the polymer/plasticizer ratio and residual moisture on disintegration time, stickiness and mechanical properties. The drug loading capacity was assessed using ketoprofen and paracetamol. Placebo ODF containing PEG400 in the 10\u201330% w/w range and 10\u201315% of residual moisture content were easy-to-handle, packed without failures and completely dissolved within 30\u202fs. NaPMM2/PEG in 80/20 ratio allowed up to 70% of paracetamol loading, which appeared as the largest value described in literature. This ODF showed good mechanical properties and disintegration time. The same formulation loaded with 25% or 50% ketoprofen (pKa\u202f=\u202f4.45) swelled without disintegrating, because of a partial protonation of NaPPM2, as verified by ATR-FTIR spectroscopy. However, the addition of 5% surfactants allowed the formulation of ODF containing 25% ketoprofen that disintegrated within one minute and guaranteed the complete drug dissolution within 5\u202fmin. All the presented data, discussed in the framework of information available on such copolymer, highlighted its versatility in the design of orodispersible dosage forms

Cyclative cleavage via solid-phase supported stabilized sulfur ylides: synthesis of macrocyclic lactones

A new synthesis of macrolactones bearing a cyclopropyl ring condensed to the macrocycle is reported via a cyclization-release strategy making use of solid-phase supported stabilized sulfur ylides

Hemodynamic and Anatomic Variations Require an Adaptable Approach during Intra-Arterial Chemotherapy for Intraocular Retinoblastoma: Alternative Routes, Strategies, and Follow-Up

BACKGROUND AND PURPOSE: Intra-arterial chemotherapy for retinoblastoma is not always a straightforward procedure, and it may require an adaptable approach. This study illustrates strategies used when the ophthalmic artery is difficult to catheterize or not visible, and it ascertains the effectiveness and safety of these strategies. MATERIALS AND METHODS: A retrospective study was performed on a series of 108 eyes affected by intraocular retinoblastoma and selected for intra-arterial chemotherapy (follow-up range, 6\N82 months). We recognized 3 different patterns of drug delivery: a fixed pattern through the ophthalmic artery, a fixed pattern through branches of the external carotid artery, and a variable pattern through either the ophthalmic or the external carotid artery. RESULTS: We performed 448 sessions of intra-arterial chemotherapy, 83.70% of them through the ophthalmic artery and 16.29% via the external carotid artery. In 24.52% of eyes, the procedure was performed at least once through branches of the external carotid artery. In 73 eyes, the pattern of drug delivery was fixed through the ophthalmic artery; for 9 eyes, it was fixed through branches of the external carotid artery; and for 17 eyes, the pattern was variable. Statistical analysis did not show any significant difference in the clinical outcome of the eyes (remission versus enucleation) treated with different patterns of drug delivery. Adverse events could not be correlated with any particular pattern. CONCLUSIONS: Alternative routes of intra-arterial chemotherapy for intraocular retinoblastoma appear in the short term as effective and safe as the traditional drug infusion through the ophthalmic artery

DogOnt - Ontology Modeling for Intelligent Domotic Environments

Abstract. Home automation has recently gained a new momentum thanks to the ever-increasing commercial availability of domotic components. In this context, researchers are working to provide interoperation mechanisms and to add intelligence on top of them. For supporting intelligent behaviors, house modeling is an essential requirement to understand current and future house states and to possibly drive more complex actions. In this paper we propose a new house modeling ontology designed to fit real world domotic system capabilities and to support interoperation between currently available and future solutions. Taking advantage of technologies developed in the context of the Semantic Web, the DogOnt ontology supports device/network independent description of houses, including both “controllable ” and architectural elements. States and functionalities are automatically associated to the modeled elements through proper inheritance mechanisms and by means of properly defined SWRL auto-completion rules which ease the modeling process, while automatic device recognition is achieved through classification reasoning.

Cinema Heritage in Europe: Preserving and Sharing Culture by Engaging with Film Exhibition and Audiences

Editoria

First AMBER/VLTI observations of hot massive stars

AMBER is the first near infrared focal instrument of the VLTI. It combines three telescopes and produces spectrally resolved interferometric measures. This paper discusses some preliminary results of the first scientific observations of AMBER with three Unit Telescopes at medium (1500) and high (12000) spectral resolution. We derive a first set of constraints on the structure of the circumstellar material around the Wolf Rayet Gamma2 Velorum and the LBV Eta Carinae