Uriach (Spain)

Abstract Extended reality (XR) promises to dramatically change the framework of scientific communication. XR offers new possibilities for creating engaging scientific content, presenting complex information, and designing immersive experiences. Scientists and communicators need to better understand interactive and immersive narratives to harness these potentials of XR. This paper proposes a multidimensional theoretical model for immersive scientific communication that evaluates the interface models of XR, analyzes its levels of reality and interaction, and identifies the dominant characteristics of the narrative. This model promotes the critical and reflective application of XR to science communication, especially citizen science projects.

IntroductionRupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses.MethodsIn this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP), reaction time (RT), spatial working memory (SWM) and visual analogue scales (VAS).ResultsExposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10–40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs) or withdrawals due to treatment–emergent adverse events (TEAEs) in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests.ConclusionsThis study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.

Clinical trials with the newer 2nd generation antihistamines in children under the age of 12 years have been performed previously but further studies are needed in order to show efficacy and safety in the most unfavourable clinical conditions such as persistent allergic rhinitis (PER). Rupatadine oral solution was developed for children with allergic rhinitis in view of its rapid onset of action and its lack of relevant side effects. These advantages were confirmed previously in a phase III study in children 6-11 years. To assess the efficacy and safety of rupatadine (RUP) oral solution in a subgroup of children between 6 and 11 years weighing ≥25 kg with PER. A subanalysis was performed from a previous placebo-controlled study carried out in patients between 6-11 years diagnosed as PER according to ARIA criteria. This analysis included patients with a positive prick test, weight ≥25 kg and basal nasal symptoms score (including rhinorrhea, nasal blockage, sneezing and nasal itching assessment) ≥24 obtained in 4 days throughout the 2-week screening period. Patients were allocated to treatment with either RUP oral solution (1 mg/ml) or placebo during 6 weeks. The dose was 5 ml of oral solution. The main efficacy endpoint was the change from baseline of the nasal (4TSS) and global symptoms (5TSS) score at 4 and 6 weeks of treatment. Furthermore the assessment of children's quality of life at 4, 6 weeks by means of PRQLQ was also evaluated. The subgroup analysed was a total of 266 randomized to rupatadine (n=131) or placebo (n=135). Table 1 summarizes the efficacy results: Rupatadine oral solution (1mg/ml) was significantly more effective than placebo in improving nasal symptoms (4TSS) at 4 and 6 weeks. This is the first clinical evidence of a H1-receptor antagonist efficacy in children between 6-11 years over 25 kg with PER.

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A new unexpected reaction of 1 -(4-fluorophenyl)-2-(4-pyridyl)ethanone 2 with 3-aminopyrazole, involving loss of a 4-pyridylmethyl group, afforded 4,6-bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine 1 in good yields. Investigation of the features of this cyclization led to the development of a new three component coupling for the synthesis of pyrazolo[3,4-b]pyridines, from a ketone, an aldehyde and a 3-aminopyrazole in the presence of acid catalysis and a protic solvent. The study of the scope of this reaction showed its remarkable versatility and its usefulness in the preparation of other bicyclic systems, such as thieno[3,2-b]pyridines, pyrrolo[3,2-b]pyridines, imidazo[4,5-b]pyridines, furo[2,3-b]pyridines, isoxazolo[5,4-b]pyridines and, isothiazolo[5,4-b]pyridines. The three component nature of this reaction makes it suitable for the preparation of combinatorial libraries since scaffold decoration can be easily achieved in one step.

A fast method for the calculation of residue contributions to protein solvation is presented. The approach uses the exposed polar and apolar surface of protein residues and has been parametrized from the fractional contributions to solvation determined from linear response theory coupled to molecular dynamics simulations. Application of the method to a large subset of proteins taken from the Protein Data Bank allowed us to compute the expected fractional solvation of residues. This information is used to discuss when a residue or a group of residues presents an uncommon solvation profile.

New spin-state-selective (S3) NMR pulse sequences exclusively applying cross-polarization schemes to achieve optimum homonuclear and heteronuclear 1H-X coherence transfer are reported for the simple and accurate measurement of the magnitude and sign of heteronuclear coupling constants for samples at natural abundance. The proposed spin-edited HCP-TOCSY experiments are based on clean heteronuclear S3 excitation, generated by simultaneous co-addition of two independent in-phase and anti-phase components created during the mixing heteronuclear J-cross-polarization (HCP) step, which is finally transferred to other protons by a conventional homonuclear TOCSY mechanism. Selective 1D and non-selective 2D approaches for the easy determination of long-range proton-carbon and proton-nitrogen coupling constants on any protonated and non-protonated heteronuclei are presented and discussed for several organic molecules.

The aim of the study was to compare the efficacy and tolerability of flutrimazole 1% powder vs. bifonazole 1% powder in treating tinea pedis. A multicentre, double blind, randomized, parallel and comparative study was conducted. Two hundred and twenty-two patients with clinically and mycologically confirmed tinea pedis were randomized to flutrimazole (n = 136) or bifonazole (n = 138) 1% powder applied twice daily for 4 weeks. The corresponding clinical cure rates were assessed at 2 and 4 weeks of treatment, and the global (clinical and mycological) cure rates were determined at the fourth week. Clinical cure rates were 83.5 and 82.4% for flutrimazole and bifonazole, respectively (95% CI: -0.0806 to 0.1009). Global cure rates were observed in 65.3 and 70.1% of patients treated with flutrimazole and bifonazole, respectively (95% CI: -0.0828 to 0.1779). Three non serious adverse events at the application site--itching (one patient per group) and dishydrotic eczema (one patient treated with flutrimazole)--were recorded during the study. These results support that flutrimazol 1% powder applied twice daily for a duration of 4 weeks is highly effective in the treatment of tinea pedis, showing a similar therapeutic profile with that of bifonazole 1% powder.