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The toxicity and efficacy of intrathecal liposomal cytarabine (LC) were evaluated in children with central nervous system (CNS) relapsed/refractory acute leukemia/lymphoma. Thirty patients (male:female ratio 21:9; median age 9.4 years) with CNS relapsed/resistant disease were treated with intrathecal LC at dosages adjusted for age. Twenty-seven (90%) patients simultaneously received systemic chemotherapy, including concurrent high-dose cytarabine or methotrexate in 21 (70%) cases. Of 28 patients evaluable for response, 25 patients (89%) achieved CNS complete remission and three (11%) partial remission. The median number of intrathecal LC administrations per patient was 4. The cerebrospinal fluid was cleared after a median of 3 intrathecal LC administrations. Neurological toxicity ≥ grade 3 occurred in four (13%) patients. No permanent sequelae were observed. The median overall survival was 20.9 months and the 5-year probability of survival was 46%. These encouraging data suggest that intrathecal LC is well tolerated and effective in children with relapsed/refractory CNS leukemia/lymphoma.

To differentiate gonadotropin deficiency from delayed puberty in teenage boys, 0.1 mg/m2 of triptorelin, a gonadotropin-releasing hormone agonist, was administered subcutaneously at 4 AM. Serum gonadotropins and testosterone levels were determined at baseline and 4 hours after the injection. The increase in blood gonadotropin and testosterone levels was significantly greater in patients with delayed puberty than in those with gonadotropin deficiency.

The paper illustrates the methodology at the basis of the design of a digital library system that enables the management of linguistic resources of curated dialect data. Since dialects are rarely recognized as official languages, first of all linguists need a dedicated information management system providing the unambiguous identification of each dialect on the basis of geographical, administrative and geolinguistic parameters. Secondly, the information management system has to be designed to allow users to search the occurrences of a specific grammatical structure (e.g. a relative clause or a particular word order). Thirdly, user-friendly graphical interfaces must give easy access to language resources and make the building of the language resources easier and distributed. This work, which stems from a project named ASIt (Atlante Sintattico d’Italia), is a first step towards the creation of a European digital library for recording and studying linguistic micro-variation.

Biologicals are important treatment options for various chronic diseases. After the introduction of the first biosimilars, animated debate arose in the scientific community about the actual benefit-risk profile of these drugs. In this context, a comparative safety evaluation of biologicals and biosimilars in clinical practice is warranted.We identified all suspected adverse drug reactions (ADRs) concerning biological/biosimilars (excluding vaccines, toxins, blood derivatives, and radio-pharmaceuticals), and further classified them into mechanistic classes. We described the frequency of biological/biosimilar class- and compound-specific ADRs by system organ class (SOC) and type of reporter. We also separately explored the traceability of biologicals and biosimilar-related ADR reports.Overall 171,201 ADR reports were collected during the observation period; 9,601 (5.6 %) of these concerned biologicals. Biological-related reports were mainly issued by hospital-based physicians (78.7 %). Most of these reports involved monoclonal antibodies and fusion proteins (66.3 %). Reported ADRs were mainly 'skin and subcutaneous tissue disorders' (21 %), 'general and administration site disorders' (17 %), and 'gastrointestinal disorders' (13.6 %). In terms of traceability, 94.8 % of biological-related reports included an identifiable product name, whilst only 8.6 % indicated the corresponding batch number. Regarding biosimilars, 298 reports were identified, with a low proportion indicating drug ineffectiveness (10.1 %).Most ADRs attributed to biologicals are 'skin and subcutaneous tissue disorders'. Anticancer monoclonal antibodies are most frequently associated with ADRs. A low proportion of ADR reports concern biosimilars.

L'articolo presenta alcune riflessioni sul valore della progettazione come processo di ricerca all’interno delle istituzioni educative, strategia che sostiene la co-costruzione delle conoscenze, valorizzando la soggettività delle singole traiettorie di apprendimento compiute da ciascun bambino all’interno di contesti di esperienza collettivi. Porta successivamente l’attenzione ai processi che caratterizzano l’approccio progettuale, sottolineando in particolare la funzione che assume il rilancio all’interno della struttura progettuale stessa, anche attraverso uno sguardo sul ruolo e le funzioni dell’adulto (educatore o insegnante).

Questo articolo presenta una rassegna di studi critici su Dietro il paesaggio, il primo libro di poesie di Andrea Zanzotto, dal 1951, anno della sua pubblicazione, al 2019. Prestando particolare attenzione alle prime rassegne, l'articolo mira a ripercorrere i passi che hanno portato al primo dibattito critico su aspetti specifici della poesia di Zanzotto, come il debito dell'autore verso l'ermetismo, l'assenza di riferimenti storici nelle sue poesie e il rapporto tra Dietro il paesaggio e la successiva pubblicazione di Zanzotto, Elegia e altri versi.

(2004). Feminism, Socialism and Research Work in a Pathology/Neuroscience Laboratory in the Late Nineteenth Century. Journal of the History of the Neurosciences: Vol. 13, No. 3, pp. 292-292.

The occurrence of epilepsy with mental retardation limited to females (EFMR; MIM 300088) has been recently associated to mutations in the PCDH19 gene, located on chromosome X and encoding for protocadherin 19. EFMR shows a rare X-linked inheritance wherein affected females may be segregating a mutation through unaffected transmitting males (Fabisiak and Erickson Clin Genet 38(5):353-358, 1990; Juberg and Hellman J Pediatr 79:726-732, 1971; Ryan et al. Nat Genet 17(1):92-95, 1997). The description of a pedigree segregating PCDH19 mutations from unaffected mothers to patients (Depienne et al. Hum Mutat 32:E1959-1975, 2011; Dibbens et al. Neurology 76:1514-1519, 2011) complicates disease inheritance and genetic counseling. In the present study, we describe a PCDH19 mutation segregating from an asymptomatic mother to an EFMR patient. In order to correlate the healthy phenotype with the genotype of the transmitting mother, we quantified in a few tissues the level of the mutant allele by real-time PCR, disclosing a somatic mosaicism. This finding has a great impact on genetic counseling.