Total Hemi-overgrowth in Pigmentary Mosaicism of the (Hypomelanosis of) Ito Type: Eight Case Reports.

Pigmentary mosaicism of the (hypomelanosis of) Ito type is an umbrella term, which includes phenotypes characterized by mosaic hypopigmentation in the form of streaks, whorls, patchy, or more bizarre skin configurations (running along the lines of Blaschko): these cutaneous patterns can manifest as an isolated skin disorder (pigmentary mosaicism of the Ito type) or as a complex malformation syndrome in association with extracutaneous anomalies (most often of the musculoskeletal and/or nervous systems) (hypomelanosis of Ito). Affected individuals are anecdotally reported to have also partial or total body hemi-overgrowth (HOG), which often causes moderate to severe complications.We studied the occurrence and features of HOG in the 114 children and adults with mosaic pigmentary disorders of the Ito type diagnosed and followed up (from 2 to 22 years; average follow-up 16 years) at our Institutions.Eight patients (5 M, 3 F; aged 4 to 25 years; median age 16 years) out of the 114 analyzed (7%) fulfilled the criteria for unilateral HOG, with differences in diameter ranging from 0.4 to 4.0 cm (upper limbs) and 1.0 to 9.0 cm (lower limbs). Moreover, among these 8 patients, 5/8 filled in the 75th to 90th percentile for height; 6/8 had associated kyphoscoliosis; and 5/8 showed cognitive delays. No tumour complications were recorded. Overall, 6/8 HOG patients presented with additional (extracutaneous) syndromic manifestations, apart from the HOG (ie, with a clinical phenotype of hypomelanosis of Ito).The present study, which includes children and adults with the longest follow-up so far recorded, confirms the association between pigmentary mosaicism of the Ito type and HOG lowering previous estimates (7% vs 16%) for HOG in the context of mosaic hypopigmentation. A careful examination, looking at subtle to moderate asymmetries and associated complications within the spectrum of these mosaic pigmentary disorders, is recommended

Forensic considerations on violent parasomnias during lifespan

Nocturnal parasomnias are a group of sleep complex manifestation that don't alter the sleep macrostructure, but when persistent during adulthood may be assume violent aspects with relevant forensic implications about the guiltiness

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas

Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. Patients and methods: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia ≥grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patient

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation

Background The primary aim was to induce a high number of pCR in early (FIGO IC, JIB + C)-and advanced (FIGO ffl—IV)—stage ovarian cancer with a surgery plus 4 cycles of cisplatin and meiphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. Patients and methods 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm iv. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accele rator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinicaJ CR or pathological PR with microscopical residual disease. Results 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMIP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c=clinical, p=pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TIF) and survival. Only 5 1/118 (43%) patients in remission received WAR Early-stage patients <=55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p= 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p= 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (3 3%) or incompleteness (3 3%) of irradiation in the majority of patients. Conclusions PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are neede

Cucurbit[n]uril binding of platinum anticancer complexes

The encapsulation of cisplatin by cucurbit[7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4′-dipyrazolylmethane (dpzm) ligand by Q[7] and cucurbit[8]uril (Q[8]) has been studied by NMR spectroscopy and molecular modelling. The NMR studies suggest that some cisplatin binds in the cucurbituril cavity, while cis-[PtCl(NH3)2(H2O)]+ only binds at the portals. Alternatively, the dpzm-linked multinuclear platinum complexes are quantitatively encapsulated within the cavities of both Q[7] and Q[8]. Upon encapsulation, the non-exchangeable proton resonances of the multinuclear platinum complexes show significant upfield shifts in 1H NMR spectra. The H3/H3* resonances shift upfield by 0.08 to 0.55 ppm, the H5/H5* shift by 0.9 to 1.6 ppm, while the methylene resonances shift by 0.74 to 0.88 ppm. The size of the resonance shift is dependent on the cavity size of the encapsulating cucurbituril, with Q[7] encapsulation producing larger shifts than Q[8]. The upfield shifts of the dpzm resonances observed upon cucurbituril encapsulation indicate that the Q[7] or Q[8] is positioned directly over the dpzm linking ligand. The terminal platinum groups of trans-[{PtCl(NH3)2}2μ-dpzm]2+ (di-Pt) and trans-[trans-{PtCl(NH3)2}2-trans-{Pt(dpzm)2(NH3)2}]4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexe

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Test of the Kolmogorov-Johnson-Mehl-Avrami picture of metastable decay in a model with microscopic dynamics

The Kolmogorov-Johnson-Mehl-Avrami (KJMA) theory for the time evolution of the order parameter in systems undergoing first-order phase transformations has been extended by Sekimoto to the level of two-point correlation functions. Here, this extended KJMA theory is applied to a kinetic Ising lattice-gas model, in which the elementary kinetic processes act on microscopic length and time scales. The theoretical framework is used to analyze data from extensive Monte Carlo simulations. The theory is inherently a mesoscopic continuum picture, and in principle it requires a large separation between the microscopic scales and the mesoscopic scales characteristic of the evolving two-phase structure. Nevertheless, we find excellent quantitative agreement with the simulations in a large parameter regime, extending remarkably far towards strong fields (large supersaturations) and correspondingly small nucleation barriers. The original KJMA theory permits direct measurement of the order parameter in the metastable phase, and using the extension to correlation functions one can also perform separate measurements of the nucleation rate and the average velocity of the convoluted interface between the metastable and stable phase regions. The values obtained for all three quantities are verified by other theoretical and computational methods. As these quantities are often difficult to measure directly during a process of phase transformation, data analysis using the extended KJMA theory may provide a useful experimental alternative.Comment: RevTex, 21 pages including 14 ps figures. Submitted to Phys. Rev. B. One misprint corrected in Eq.(C1

Rilevazione nazionale in tema di formazione specifica di medicina generale in Italia

Physicians have to get a \u201cspecific\u201d diploma attending a threeyear training course provided by each regional health service in order to practice as General Practitioners in Italy. In the last years, there has been an ongoing debate about the need to evolve the specific regional courses into integrated specialization training courses, organized and managed by universities with the contribution of regional health services. The Italian Junior Doctors Association and the Giotto Movement carried out a national survey with the aim to identify strengths and weaknesses of the specific regional training courses. Three-hundred-two junior General Practitioners in training (61,2% females) answered to a web administered questionnaire. Only about half of the recruited trainees has defined as at least \u201csufficient\u201d the training provided by the regional courses. The survey documented in the Italian General Practitioners trainees the need to satisfy an educational demand in order to implement their primary care and general practice skills. In conclusion, this cross-sectional study provided sufficient evidences supporting the evolution of the regional training courses into general practice and primary care specialization schools

Giacomo Serpotta e il "pareggiamento delle arti": la decorazione degli oratori fra manipolazione vitalistica e vocazione classicista

ABSTRACT GIACOMO SERPOTTA AND THE “EQUALIZATION OF THE ARTS”: DECORATION OF THE ORATORIES BETWEEN VITALISTIC MANIPULATION AND CLASSICIST VOCATION Ettore Sessa The value of the whole of Giacomo Serpotta's artistic vision in the orchestration of the figu¬rative apparatuses of his oratories was certainly one of the principal primers of his historical-critical raising in the modernist period. In 1901 Mauceri and in 1911 Ricci and Basile heighten a profile of it, however synthetic, of angling and above all of different breath from the rediscovery realized in positivist age. Classifiable, in fact, among the eighteenth century precedents of Gesamtkunstwerk aesthetical plant (according to a rather diffused custom within the artistic historiography of modernist culturaI area or of decadentist origin, as in different formalistic demonstrations of the wealthiest society Belle Époque) the progress of Serpottas artistic way towards tangible expressions of the idea of «the whole work of art» has a unmistakable im¬print of his and, at the same time, a feasibility thanks to the plasticism of gestures and to the uni¬tary multiplicity of his modeled. In his oratories arrangements the "realist" component, not exempted from hedonistic sensual witty remarks, acts on a foundation of Hellenic taste (also in the use of profiles and architectural elements). With wise modulation and with dosing diversified for intensity, according the nature of the subjects, combines history (see the «teatrini» with perspective sceneries, among which the Lepanto battle), micro history (from feminine allegorical subjects, to attractive dames modernly adorned with ends and brocades, to "picciotti" proudly ragged and to the anecdotal of the daily life), mysticism (from the devotional subjects to the allegories of the virtues), obscurity (from numerological components to philosophical attributes) and, finally, mythology (from the allegorical correspondences between Christianity and paganism to classical simbology). Despite the actual halving of this group of oratories (was destroyed by traumatic events as earthquakes and war actions, or by villainous demolitions big part of Serpottas works, among which the SS. Sacrament oratories to Kalsa and those of Saint Maria del Ponticello), the comparison among the palermitan examples reached us entire allows the individualization of the characters of originality typical of the generaI composition, over that of those figurative unanimously accredited among the most valid of the late- Baroque European sculpture. The typical scheme of these oratories, places with a strong secular imprint (predisposed as for cultural reunions how as for the preclusive congregational assemblies, to which the only ones not admitted affiliate were the artists), has as constants: the hall with a rectangular plant; the skiff or pavilion vault with plaster decorations dissimulating the constructive geometry; the sculptural wall register above of a high plinth; windows on the greatest sides (in number of three); two doors in the counterfacade, originally with desk for the assemblies in central position, below the principal devotional allegorical composition. The first oratory to which Giacomo Serpotta imposes an unitary imprint, except the cappellone only defined between 1717 and the following year) is that of SS. Rosary in S. Cita; he has worked since 1685 to 1688 on behalf of SS. Rosary Company. Serpotta is twenty nine, but already since almost ten years, after the apprenticeship with subordinate roles, he showed himself almost beginning in mute with the decorations of Madonna of the Pity church in Monreale, where he operated like Procopio De' Ferrari's collaborator, and perhaps with his interventions in 1678 in the lateral walls of S. Mercurio oratory, to which follow the 1679 decoration works in the Charity oratory in St. Bartholomeo of the Incurable people (no more existing), perhaps S. Pietro and S. Paolo statues dating back to 1680 for the greatest altar in Gancia church, the marble model for Charles H's equestrian monument for Messina (then realized in 1684) and during the two years 1683-1684 the scenic decorations for the transept altars of Carmine Maggiore church (where he collaborates with his brother Giuseppe and realizes the couples of twisted columns gilded and commented by a theory of plaster miniature scenes disposed according to a spiral development). Immediately after S. Cita oratory he realized, between 1688 and 1691, the decorative apparatuses of the Sacrament oratory in S. Nicolò to Kalsa (destroyed because of 1823 earthquake). Only eight years after the completion of this work (about which it was hypothesized that it were an advancement in comparison to the intervention in S. Cita) Giacomo Serpotta is entrusted by S. Francesco from Assisi and S. Lorenzo Companies to realize the complex allegorical and explanatory cycle of the plasters of S. Lorenzo orato¬ry. He worked partly on Giacomo Amato's sketches (to which are probably owed the reform interventions that confer to this oratory a great architectural "squaring" in comparison to others), completing the presbytery within 1706, while already from 1701 he is busy in the definition of the walls. In 1703 he began the counter facade with the monumental wall framework and high-relief representation of St. Lorenzo Martyrdom