The Effect of Simple Melodic Lines on Aesthetic Experience: Brain Response to Structural Manipulations

This fMRI study investigates the effect of melody on aesthetic experience in listeners na \u308\u131ve to formal musical knowledge. Using simple melodic lines, whose syntactic structure was manipulated, we created systematic acoustic dissonance. Two stimulus categories were created: canonical (syntactically \u201ccorrect,\u201d in the Western culture) and modified (made of an altered version of the canonical melodies). The stimuli were presented under two tasks: listening and aesthetic judgment. Data were analyzed as a function of stimulus structure (canonical and modified) and stimulus aesthetics, as appraised by each participant during scanning. The critical contrast modified versus canonical stimuli produced enhanced activation of deep temporal regions, including the parahippocampus, suggesting that melody manipulation induced feelings of unpleasantness in the listeners. This was supported by our behavioral data indicating decreased aesthetic preference for the modified melodies. Medial temporal activation could also have been evoked by stimulus structural novelty determining increased memory load for the modified stimuli. The analysis of melodies judged as beautiful revealed that aesthetic judgment of simple melodies relied on a fine-structural analysis of the stimuli subserved by a left frontal activation and, possibly, on meaning attribution at the charge of right superior temporal sulcus for increasingly pleasurable stimul

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered

Blockade of nociceptive sensory afferent activity of the rat knee joint by the bradykinin B2 receptor antagonist fasitibant

[Objective] The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia.[Methods] Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test.[Results] BK (100 μM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 μM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 μg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug.[Conclusions] Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.This work was supported by grants from Spanish MICINN BFU2009-07835 to AG, BFU2008-04425 to CB and CONSOLIDER-INGENIO 2010 CSD2007-00023.Peer reviewe

Booster immunization with a fractional dose of Prevnar 13 affects cell-mediated immune response but not humoral immunity in CD-1 mice

Achieving durable protective immunity following vaccination is dependent on many factors, including vaccine composition and antigen dose, and it has been investigated for various types of vaccines. Aim of the present study was to investigate the overall immune response elicited by two different booster doses in CD-1 mice, by exploiting the largely used 13-valent pneumococcal conjugate vaccine Prevnar 13® (PCV13). Immunization was performed by two primary doses of PCV13 two weeks apart, and a full or fractional (1/5) booster dose on week 10. Serotype-specific antibody titer, avidity, and opsonophagocytic activity were evaluated one week later, and compared to cell-mediated immunity (CMI) responses determined as the frequency of cytokines producing splenocytes by in vitro recall with the antigens (carrier protein and polysaccharides). Data showed that regardless of the booster dose, a comparable humoral response was produced, characterized by similar amounts of serotype-specific antibodies, with analog avidity and opsonophagocytic properties. On the other hand, when CMI was evaluated, the presence of CRM197-specific IL-5 and IL-2 producing cells was evident in splenocytes from mice immunized with the full dose, while in those immunized with the fractional booster dose, IFN-γ producing cells responsive to both protein and polysaccharide antigens were significantly increased, whereas the number of IL-5 and IL-2 positive cells remained unaffected. Overall the present findings show that PCV13 humoral response in mice is associated to a Th2 predominant response at the full booster dose, while the fractional one favors a mixed Th1/Th2 response, suggesting an important role of CMI besides measurement of functional protective antibodies, as an additional and important key information in vaccine development

Bradykinin antagonists modified with dipeptide mimetic β-turn inducers

Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure–activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic b-turn inducers