Juegos dialógicos del discurso cervantino: la palabra de los clásicos antiguos

Il discorso narrativo di Cervantes è guidato dalle nuove tecniche retoriche sviluppate nel Rinascimento. La sua opera si presenta dunque come una serie di esemplari scelte artistiche nel campo del romanzo, della letteratura drammatica e della satira. Posto di fronte al problema dell' imitatio dei generi classici, Cervantes procede solitamente per contaminazione con altre forme tipiche dell suo tempo come la pastorale, la novella di matrice greca o boccacciana, fino ai romanzi cavallereschi. Lo stesso procedimento guida la composizione del discorso appropriato per ogni genere: Cervantes combina l'imitazione di frasi o espressioni tratte dalle sue fonti con tecniche retoriche di sua invenzione. Questo metodo si imparava a scuola, mediante la copia dei dicta antichi e la loro memorizzazione o archiviazione nei codices excerptorii degli alunni. Gli scrittori professionisti potevano così contare su un repertorio di topoi, sententiae, exempla, aforismi e apoftegmi che fungeva da guida nel campo dell'elocutio ma anche in quello dell'inventio. Le citazioni degli autori antichi avevano così un valore ideologico per chi scriveva o leggeva un testo letterario, trasmettendo le idee dei classici a proposito dell'universo, del corpo umano, dello spirito e delle emozioni, considerate allora come universali. Nel saggio si analizzano da questo punto di vista alcune sezioni del Quijote, della Galatea, di qualche Novela ejemplar e del Persiles, confermando la conoscenza di prima mano che Cervantes aveva dei classici.Cervantes' narrative discourse was built according to the new rhetorical practices that developed since the Renaissance. Thus, his work reads as a model of the artistic options that he appropriated in the realms of fiction, drama and satire. In the imitatio of classical genres, Cervantes practices contaminatio with other models typical of his age – from pastoral to the Greek novel, from books of chivalry to Boccaccio's novella. The same method is applied to the construction of each genre's discourse, in which he combines expressions taken from his sources with rhetorical devices of his own creation. This method was learned in school. It included the recopilation of ancient dicta, which students memorized or copied in their codices excerptorii. Future professional writers would have at hand a first repertory of topoi, sententiae, exempla, aphorisms and apothegms, which led authors in the realms of elocutio and inventio. These citations of the antiqui auctores were also important from an ideological point of view, since they transmitted their ideas about the universe, the human body, the spirit or human emotions, which were understood as universals at the time. In this paper are analyzed from this perspective several sections of the Quijote, of the Galatea, of some Exemplary Novel or the Persiles, which also confirm Cervantes's familiarity with the many classical works that he personally read

Congenital long QT syndrome

Congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by a prolongation of the QT interval at basal ECG and by a high risk of life-threatening arrhythmias. Disease prevalence is estimated at close to 1 in 2,500 live births.The two cardinal manifestations of LQTS are syncopal episodes, that may lead to cardiac arrest and sudden cardiac death, and electrocardiographic abnormalities, including prolongation of the QT interval and T wave abnormalities. The genetic basis of the disease was identified in the mid-nineties and all the LQTS genes identified so far encode cardiac ion channel subunits or proteins involved in modulating ionic currents. Mutations in these genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1c, CAV3, SCN5A, SCN4B) cause the disease by prolonging the duration of the action potential. The most prevalent LQTS variant (LQT1) is caused by mutations in the KCNQ1 gene, with approximately half of the genotyped patients carrying KCNQ1 mutations.Given the characteristic features of LQTS, the typical cases present no diagnostic difficulties for physicians aware of the disease. However, borderline cases are more complex and require the evaluation of various electrocardiographic, clinical, and familial findings, as proposed in specific diagnostic criteria. Additionally, molecular screening is now part of the diagnostic process.Treatment should always begin with beta-blockers, unless there are valid contraindications. If the patient has one more syncope despite a full dose beta-blockade, left cardiac sympathetic denervation (LCSD) should be performed without hesitation and implantable cardioverter defibrillator (ICD) therapy should be considered with the final decision being based on the individual patient characteristics (age, sex, clinical history, genetic subgroup including mutation-specific features in some cases, presence of ECG signs - including 24-hour Holter recordings - indicating high electrical instability).The prognosis of the disease is usually good in patients that are correctly diagnosed and treated. However, there are a few exceptions: patients with Timothy syndrome, patients with Jervell Lange-Nielsen syndrome carrying KCNQ1 mutations and LQT3 patients with 2:1 atrio-ventricular block and very early occurrence of cardiac arrhythmias

Congenital Short QT Syndrome

The Short QT Syndrome is a recently described new genetic disorder, characterized by abnormally short QT interval, paroxysmal atrial fibrillation and life threatening ventricular arrhythmias. This autosomal dominant syndrome can afflict infants, children, or young adults; often a remarkable family background of cardiac sudden death is elucidated. At electrophysiological study, short atrial and ventricular refractory periods are found, with atrial fibrillation and polymorphic ventricular tachycardia easily induced by programmed electrical stimulation. Gain of function mutations in three genes encoding K+ channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for Ikr (SQT1), KCNQ1 for Iks (SQT2) and KCNJ2 for Ik1 (SQT3). The currently suggested therapeutic strategy is an ICD implantation, although many concerns exist for asymptomatic patients, especially in pediatric age. Pharmacological treatment is still under evaluation; quinidine has shown to prolong QT and reduce the inducibility of ventricular arrhythmias, but awaits additional confirmatory clinical data

Strange-Face-in-the-Mirror Illusion and Schizotypy During Adolescence

Patients with schizophrenia can sometimes report strange face illusions when staring at themselves in the mirror; such experiences have been conceptualized as anomalous self-experiences that can be experienced with a varying degree of depersonalization. During adolescence, anomalous self-experiences can also be indicative of increased risk to develop schizophrenia-spectrum disorders. To date however, the Mirror-Gazing test (MGT), an experimentally validated experiment to evaluate the propensity of strange face illusions in nonclinical and clinical adults, has yet to be investigated in an adolescent sample. The first goal of the present study was to examine experimentally induced self-face illusions in a nonclinical sample of adolescents, using the MGT. The second goal was to investigate whether dimensions of adolescent trait schizotypy were differentially related to phenomena arising during the MGT. One hundred and ten community adolescents (59 male) aged from 12 to 19 years (mean age = 16.31, SD age = 1.77) completed the MGT and Schizotypal Personality Questionnaire. The results yielded 4 types of strange face illusions; 2 types of illusions (slight change of light/color [20%] and own face deformation [45.5%]) lacked depersonalization-like phenomena (no identity change), while 2 other types (vision of other identity [27.3%], and vision of non-human identity [7.3%]) contained clear depersonalization-like phenomena. Furthermore, the disorganization dimension of schizotypy associated negatively with time of first illusion (first press), and positively with frequency of illusions during the MGT. Statistically significant differences on positive and disorganized schizotypy were found when comparing groups on the basis of degree of depersonalization-like phenomena (from slight color changes to non-human visions). Similarly to experimentally induced self-face illusions in patients with schizophrenia, such illusions in a group of nonclinical adolescents present significant associations to schizotypy dimension

Arrhythmogenic Calmodulin Mutations Disrupt Intracellular Cardiomyocyte Ca\u3csup\u3e2+\u3c/sup\u3e Regulation by Distinct Mechanisms

BACKGROUND: Calmodulin (CaM) mutations have been identified recently in subjects with congenital long QT syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT), but the mechanisms responsible for these divergent arrhythmia-susceptibility syndromes in this context are unknown. We tested the hypothesis that LQTS-associated CaM mutants disrupt Ca2+ homeostasis in developing cardiomyocytes possibly by affecting either late Na current or Ca2+-dependent inactivation of L-type Ca2+ current. METHODS AND RESULTS: We coexpressed CaM mutants with the human cardiac Na channel (NaV1.5) in tsA201 cells, and we used mammalian fetal ventricular cardiomyocytes to investigate LQTS- and CPVT-associated CaM mutations (LQTS- and CPVT-CaM). LQTS-CaM mutants do not consistently affect L-type Na current in heterologous cells or native cardiomyocytes, suggesting that the Na channel does not contribute to LQTS pathogenesis in the context of CaM mutations. LQTS-CaM mutants (D96V, D130G, F142L) impaired Ca2+-dependent inactivation, whereas the CPVT-CaM mutant N54I had no effect on Ca2+-dependent inactivation. LQTS-CaM mutants led to loss of Ca2+-transient entrainment with the rank order from greatest to least effect: CaM-D130G~CaM-D96V\u3e\u3eCaM-F142L. This rank order follows measured Ca2+-CaM affinities for wild-type and mutant CaM. Acute isoproterenol restored entrainment for CaM-130G and CaM-D96V but caused irreversible cytosolic Ca2+ overload for cells expressing a CPVT-CaM mutant. CONCLUSIONS: CaM mutations associated with LQTS may not affect L-type Na+ current but may evoke defective Ca2+-dependent inactivation of L-type Ca2+ current

Generation of the human induced pluripotent stem cell (hiPSC) line PSMi003-A from a patient affected by an autosomal recessive form of Long QT Syndrome type 1

Abstract We generated human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a 51 years old female patient homozygous for the mutation c.535 G>A p.G179S on the KCNQ1 gene, causing a severe form of autosomal recessive Long QT Syndrome type 1 (AR-LQT1), not associated with deafness. The hiPSCs, generated using four retroviruses each encoding for a reprogramming factor OCT4, SOX2, KLF4, cMYC, are pluripotent and can differentiate into spontaneously beating cardiomyocytes (hiPSC-CMs)

Generation of the human induced pluripotent stem cell (hiPSC) line PSMi006-A from a patient affected by an autosomal recessive form of Long QT Syndrome type 1

We generated human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a 40 years old female patient homozygous for the mutation c.535 G > A p.G179S on the KCNQ1 gene, causing a severe form of autosomal recessive Long QT Syndrome type 1 (AR-LQT1). The hiPSCs, generated using classical approach of the four retroviruses enconding the reprogramming factors OCT4, SOX2, cMYC and KLF4, display pluripotent stem cell characteristics, and differentiate into cell lineages of all three germ layers: endoderm, mesoderm and ectoderm. Keywords: Endoderm, Mesoderm, Ectoder

NOS1AP polymorphisms reduce NOS1 activity and interact with prolonged repolarization in arrhythmogenesis

Aims  NOS1AP single-nucleotide polymorphisms (SNPs) correlate with QT prolongation and cardiac sudden death in patients affected by long QT syndrome type 1 (LQT1). NOS1AP targets NOS1 to intracellular effectors. We hypothesize that NOS1AP SNPs cause NOS1 dysfunction and this may converge with prolonged action-potential duration (APD) to facilitate arrhythmias. Here we test (i) the effects of NOS1 inhibition and their interaction with prolonged APD in a guinea pig cardiomyocyte (GP-CMs) LQT1 model; (ii) whether pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from LQT1 patients differing for NOS1AP variants and mutation penetrance display a phenotype compatible with NOS1 deficiency. Methods and results  In GP-CMs, NOS1 was inhibited by S-Methyl-L-thiocitrulline acetate (SMTC) or Vinyl-L-NIO hydrochloride (L-VNIO); LQT1 was mimicked by IKs blockade (JNJ303) and β-adrenergic stimulation (isoproterenol). hiPSC-CMs were obtained from symptomatic (S) and asymptomatic (AS) KCNQ1-A341V carriers, harbouring the minor and major alleles of NOS1AP SNPs (rs16847548 and rs4657139), respectively. In GP-CMs, NOS1 inhibition prolonged APD, enhanced ICaL and INaL, slowed Ca2+ decay, and induced delayed afterdepolarizations. Under action-potential clamp, switching to shorter APD suppressed ‘transient inward current’ events induced by NOS1 inhibition and reduced cytosolic Ca2+. In S (vs. AS) hiPSC-CMs, APD was longer and ICaL larger; NOS1AP and NOS1 expression and co-localization were decreased. Conclusion  The minor NOS1AP alleles are associated with NOS1 loss of function. The latter likely contributes to APD prolongation in LQT1 and converges with it to perturb Ca2+ handling. This establishes a mechanistic link between NOS1AP SNPs and aggravation of the arrhythmia phenotype in prolonged repolarization syndromes