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Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.

Abstract To evaluate the influence of rewetting solutions on bond strength to root dentin of conventional gutta-percha (GP) or niobium phosphate glass-based gutta-percha (GNb) associated with a bioceramic sealer. The root canals of 80 human mandibular premolars were prepared using nickel-titanium instruments and irrigation with sodium hypochlorite and EDTA. The teeth were randomly divided into four groups according to the gutta-percha used: GNb or GP associated with EndoSequence BC Sealer (BC) and the solution for rewetting dentin before filling (distilled water; phosphate buffer saline solution - PBS; simulated body fluid – SBF; or no solution). The root canals were filled with a single cone using warm vertical condensation. Micropush-out bond strengths associated with the filling materials in slices from middle root thirds was determined 30 days after root filling. The failure mode was analyzed with stereoscopic lens. The data were statistically analyzed by two-way ANOVA and Holm-Sidak test (p < 0.05). There was significant difference in the types of gutta-percha (p < 0.001) and in the different rewetting solutions (p = 0.003). The interaction between gutta-percha and rewetting solutions was not significant (p = 0.53). The SBF solution provided an increase in bond strength for both gutta-percha solutions. The GNb+BC (3.42 MPa) association increased bond strength when compared with GP+BC (2.0 MPa). The use of SBF as a dentin rewetting solution increased bond strength in the groups studied. Association of GNb with bioceramic sealer was beneficial, increasing the bond strength to dentin when compared with the association with GP.

Introduction: Liver transplantation is considered the best treatment for irreversible liver disease. Due to the complexity of the procedure generally multiple blood transfusions are required. One option to reduce this need is the use of Cell Saver providing blood cell recovery and reinfusion. Purpose: to evaluate mortality in the number of washed red blood cell units recovered by Cell Saver and perioperative mortality. Methods: Data collection of transplant patients using CellSaver on the period from July 2014 to February 2017. Results: Performed 56 liver transplants, the diagnosis prevalent was liver cirrhosis by hepatitis C virus (37,5%). Of these 45 (80,4%) of the transplants used Cell Saver, which had a median MELD of 24,5 (range 7-50). Taking into account the use of Cell Saver in washed red blood cell units and recovered notes a median of four (range 1-45). 12 died (26,7%), the average of these MELD was 25,5 (range 1-50) and the use of washed red blood cell and recovered was a median of 4,5. Conclusion: Patients who died used a similar amount of washed and recovered erythrocyte units.

After 25 years, evaluation of minimal residual disease (MRD) in follicular lymphoma (FL) has become a standardized technique frequently integrated in clinical trials for its consistent and independent prognostic significance. Achievement of a sustained MRD negativity is a marker of treatment sensibility that has been associated with excellent clinical outcome in terms of clinical response and progression-free survival, independently from the employed therapy. However, no survival advantages has been reported for MRD negative patients and despite the compelling results of clinical trials, MRD evaluation has currently no role in clinical practice. Ongoing clinical trials will help in clarifying the potential setting in which MRD monitoring may have a routine clinical application i.e. allowing de-escalation of standard maintenance therapy in very low risk patients. In this review the clinical implications of MRD monitoring in Rituximab-era are discussed in light of the current treatment paradigms most aimed at reducing toxicities, and the response definition that now routinely integrates PET scan. Keywords: Follicular lymphoma, minimal residual disease, molecular remission, outcome prediction

L’articolo esamina il caso della Pedia de Cyro di Boiardo dimostrando come il volgarizzamento raffrontato all’Historia de Cyri vita, la traduzione latina di Poggio Bracciolini della Ciropedia di Senofonte, offra un osservatorio privilegiato sul modo di lavorare del conte di Scandiano: poiché il testo è stato lasciato ad uno stadio intermedio tra l’abbozzo e la limatura definitiva, è stato possibile rintracciarvi i luoghi dell’intervento boiardesco e la sua riscrittura in chiave moderna. Il volgarizzamento presenta una narrazione meno vicina all’impianto per lo più dialogico dell’originale, mantenuto prevalentemente anche in Poggio, e più sciolta, che pone al centro del racconto l’azione. La riscrittura di interi passi permette di precisare il modo in cui Boiardo è intervenuto sulla primitiva traduzione del suo segretario, amplificandola con dovizia di particolari a partire da stilemi boccacciani, per trasformare il tono epico della vicenda in timbro cavalleresco e patetico. Si sono presentati alcuni casi significativi dell’azione versoria e dell’elaborazione letteraria del conte, proponendone sempre l’analisi linguistico-retorica, a dimostrazione di come la riscrittura boiardesca abbia eliminato il lato epico, ma anche divertente e lepido della Ciropedia, mantenuto da Poggio, a favore di un’atmosfera più patetica e moraleggiante, maggiormente consona all’interesse del duca di Ferrara. This article examines how Boiardo’s vernacular translation of the Pedia de Cyro offers insight into the Count of Scandiano’s modus operandi: whilst being somewhere between the draft and polishing stage, the Boiardo text reveals various degrees of translation. The vernacular translation presents a narrative far from the more dialogical structure of the original work and reproposed by Poggio Bracciolini in his translation. In fact, Boiardo’s work appears to be more light and free and places action at its core. Moreover, the presence of a number of entirely rewritten passages allows one to view the way in which Boiardo intervened on his Secretary’s translation, amplifying it in detail with a Boccaccio-like style, resulting in a more chivalrous tone. The Count of Scandiano’s Pedia de Cyro reveals his exposure to various kinds of classical narrative and provides some sense of the Ferrarese cultural setting in which experimentation with narrative was encouraged. In short, Boiardo attempts to fuse elements of the classical and vernacular tradition bringing together high and low culture in a narrative context by proposing a strongly linguistic and rhetorical version favoring a more pathetic and moralizing tone rather than one of humor and wit present in Poggio’s translation of Xenophon’s Cyropaedia.

Objetivo: Avaliar a eficácia de um programa interdisciplinar semanal (PIS) composto de atividades educativas, terapias físicas, alongamento, ergonomia, orientações posturais combinado com estratégias cognitivas e comportamentais e abordagens de aspectos psicossociais e ocupacionais, a fim de determinar se esta intervenção seria efetiva em curto e médio prazos para melhora dos sintomas destes pacientes. Casuística e métodos: Trata-se de um estudo unicêntrico, randomizado, simples cego e controlado com amostra de um grupo-teste (T), com diagnóstico de SFM (n = 12), e de um grupo-controle (C) submetido a interconsulta na Clínica da Dor (n = 15). Os instrumentos utilizados em dois momentos distintos foram: Questionário de Impacto de Fibromialgia (FIQ), Escala Visual Analógica (EVA) e Protocolo Pós-Sono (PSI). Para avaliar a qualidade de vida, foi utilizado o Questionário SF-12. Resultados: Na amostra dos dois grupos houve predomínio do gênero feminino, média de idade de 42,5±9,8 anos, 43% casados e média de escolaridade de 8,3±4,5 anos. Foi relatado um tempo médio de dor de 4,2 anos e uma média de dois anos para o diagnóstico de SFM no grupo T. Houve diferença estatística entre os grupos, em relação à eficácia pós-intervenção do PIS, em quase todos os desfechos analisados. Conclusão: Verificou-se que o programa interdisciplinar semanal (PIS) contribuiu para melhora da qualidade de vida dos pacientes fibromiálgicos.

Modern analytical applications of liquid chromatography require columns with higher and higher efficiencies. In this work, the general rate model (GRM) of chromatography is used for the analysis of the efficiency of core-shell phases having two porous layers with different structures and/or surface chemistries. The solution of the GRM in the Laplace domain allows for the calculation of moments of elution curves (retention time and peak width), which are used for the analysis of the efficiency of bi-layer particles with and without a non-porous core. The results demonstrate that bi-layer structures can offer higher separation power than that of the two layers alone if the inner layer has smaller surface coverage (retentivity) and the pore size and pore diffusion of the outer layer is either equal to or higher than that of the inner layer. Even in the case of core-shell phases, there is an increase in resolution by applying the bi-layer structure; however, we can always find a mono-layer core-shell particle structure with a larger core size that provides better resolution. At the optimal core size, the resolution cannot be further improved by applying a bi-layer structure. However, in case of the most widely produced general-purpose core-shell particles, where the core is ∼70% of the particle diameter, a 15−20% gain of resolution can be obtained by using well-designed and optimized bi-layer core-shell phases.

Objective: To explore the contributions of genetic and environmental influences to individual variation and covariation of the Child Behavior Checklist (CBCL) DSM-oriented scales (DOS) originally proposed by Achenbach and associates in 2001. Method: A classic twin study of 398 twin pairs ages 8 to 17 years belonging to the population-based Italian Twin Registry, assessed by parents using the CBCL for Ages 6 to 18 (CBCL/6-18). Results: Univariate analyses showed that compared with the classic CBCL/6-18 empirical subscales, the DOS have higher heritability (lowest 0.54 for Anxiety Problems, highest 0.71 for Conduct Problems) and simpler causal structure in that the phenotypic variance was satisfactorily explained by additive genetic and unique environmental factors only. Multivariate analyses showed that the causes of phenotypic correlation among the different DOS can be attributed to one common genetic factor and to two idiosyncratic environmental factors, each loading differently on the Internalizing (Anxiety and Affective Problems) and the Externalizing(Attention-Deficit/Hyperactivity, Oppositional Defiant, and Conduct Problems) CBCL/6-18 DOS. Conclusions: Several common risk factors of both genetic and environmental nature can simultaneously affect a child's proneness to develop the psychopathological signs and symptoms captured by the CBCL/6-18 DOS. (Contains 4 tables and 1 figure.)

Maria Esposito,1 Beatrice Gallai,2 Lucia Parisi,3 Michele Roccella,3 Rosa Marotta,4 Serena Marianna Lavano,4 Antonella Gritti,5 Giovanni Mazzotta,6 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical, and Preventive Medicine, Second University of Naples, Naples, 2Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, 3Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, 4Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, 5Suor Orsola Benincasa University, Naples, 6Unit of Child and Adolescent Neuropsychiatry, Azienda Sanitaria Locale 4, Terni, ItalyBackground: Migraine without aura is a primary headache which is frequent and disabling in the developmental age group. No reports are available concerning the prevalence and impact of migraine in children on the degree of stress experienced by parents. The aim of this study was to evaluate the prevalence of maternal stress in a large pediatric sample of individuals affected by migraine without aura.Methods: The study population consisted of 218 children (112 boys, 106 girls) of mean age 8.32 ± 2.06 (range 6–13) years suffering from migraine without aura and a control group of 405 typical developing children (207 boys, 198 girls) of mean age 8.54 ± 2.47 years. Mothers of children in each group answered the Parent Stress Index-Short Form (PSI-SF) questionnaire to assess parental stress levels.Results: The two groups were matched for age (P = 0.262), gender (P = 0.983), and body mass index adjusted for age (P = 0.106). Mothers of children with migraine without aura reported higher mean PSI-SF scores related to the Parental Distress domain (P < 0.001), Dysfunctional Parent-Child Interaction domain (P < 0.001), Difficult Child subscale (P < 0.001), and Total Stress domain than mothers of controls (P < 0.001). No differences between the two groups were found for Defensive Responding subscale scores.Conclusion: Our study may be the first to highlight the presence of high levels of stress in parents of children affected by migraine without aura.Keywords: parental stress, childhood migraine, migraine without aura, children

Infantile hemangiomas (IH) complicated by ulceration, disfigurement, functional impairment or life-threatening conditions need early, safe and effective treatment. This study explores the impact of propranolol on complicated IH. We report our experience of 62 patients treated with oral propranolol for complicated IH. The effect of propranolol was assessed using a score on a visual analogue scale integrated with echo, magnetic resonance or endoscopic findings. The average age at the beginning of the treatment was seven months [standard deviation (SD)±8.9], with a median of four months (range 1-53 months). The average age at the end of the treatment was 15 months (SD±8.4), with a median of 13 months (range 7-59 months). The mean treatment length was eight months (SD±3.2). Oral propranolol was successful in 95.2% of the patients in reducing the volume, the intensity of color and the elevation of IH. Statistically significant improvement of IH volume was observed in the first two months of therapy (P≤0.001), and between the second month and the end of the treatment (P

weight on social cost. An improved resources utilization could promote a reduction of the new hospitalization and a of medical costs. Working hypotesis: To analyze a model of increased utilization of our Cardiac Rehabilitation (CR) Unit, aiming at improving the cost/profit ratio through a better use of resources and a better assignment of care. With a reduction of average length of stay in the Operative Units for acute patients, we could promote a demand of post-acute hospitalization of 950.7 days of hospitalization that could be assigned to Cardiologic Rehabilitation Unit. Results: With the transfer of patients the utilization rate of CR would increase to 97%. With a mean period in bed of 15.3 days we could hospitalize 62 additional patients and the total margin of contribution would became positive: 69.817 euro. The break even analysis applied to costs and returns of the Unit shows a further indication to increase the hospitalization number in CR Unit with patients transfered from acute patient units. Under the same costs the recovery of efficiency leads to a reduction of variable costs. In the same time there is an increase of returns due to an increase of mean value for case and an increase of services. Conclusion: The increase in the efficiency in the utilization of CR Unit leads to an increase of the Hospital efficiency. The transfer of patients from acute units to CR Unit would allow an increased hospitalization rate for acute patients without requiring additional resources.

Maria Esposito,1 Antonio Pascotto,1 Beatrice Gallai,3 Lucia Parisi,2 Michele Roccella,2 Rosa Marotta,4 Serena Marianna Lavano,4 Antonella Gritti,5 Giovanni Mazzotta,6 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Second University of Naples, Naples, 2Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, 4Department of Psychiatry, “Magna Graecia” University of Catanzaro, Catanzaro, 5Suor Orsola Benincasa University, Napoli, 6Unit of Child and Adolescent Neuropsychiatry, Azienda Sanitaria Locale 4, Terni, ItalyBackground: The purpose of this study was to assess the cognitive functioning of children affected by headache, pinpointing the differences in intelligence style between subjects affected by migraine without aura and subjects with tension-type headache.Methods: The study population consisted of 147 children (mean age 10.82 ± 2.17 years) with headache, recruited from the Headache Center for Developmental Age, Child and Adolescent Neuropsychiatry Clinic, Second University of Naples. Cognitive profiling was performed using Weschler Intelligence Scale for Children Third Edition throughout the sample. According to the International Classification of Headache Disorders II criteria for pediatric age, subjects were divided into a migraine without aura group (n = 75; 43 boys, 32 girls) and a tension-type headache group (n = 72; 49 boys, 23 girls). The results were compared with the findings obtained from a sample of 137 healthy control subjects recruited from schools in the Campania region, matched for age and gender.Results: No difference in full intelligence quotient was found between the groups, but the children with tension-type headache had a lower verbal intelligence quotient and a higher performance intelligence quotient than the healthy controls and children with migraine. Factor analysis data showed that the children with migraine seemed to have lower perceptual organization than the children affected by tension-type headache.Conclusion: To our knowledge, studies on cognitive functioning in children affected by headache in the interictal phase are scarce, and our results suggest a new perspective in understanding of the neuropsychological aspects of young patients affected by headaches.Keywords: childhood headache, intelligence quotient, Weschler Intelligence Scale for Children Third Edition, intelligence, migraine

OBJETIVO: Determinar a concordância da medida da resistência das vias aéreas (RVA) pela técnica interrupter resistance (Rint, resistência do interruptor) com a do método pletismográfico para fins de aplicabilidade clínica. MÉTODOS: A técnica Rint foi realizada com os pacientes em posição sentada, em expiração, utilizando clipe nasal e com suporte das bochechas. O exame pletismográfico foi realizado de acordo com protocolos padronizados. As medidas foram realizadas antes e após a administração inalatória de um broncodilatador via spray dosimetrado com espaçador. RESULTADOS: Avaliamos 99 pacientes consecutivos encaminhados para o Hospital de Clínicas de Porto Alegre, Porto Alegre (RS), para a realização de testes de função pulmonar, com idades entre 18 e 82 anos. Desses, 52 eram mulheres. Houve boa concordância entre os métodos (r = 0,8; coeficiente de correlação intraclasse = 0,8) nos pacientes com VEF1 > 60% do previsto. Os valores de Rint foram menores que os da RVA por pletismografia em indivíduos mais graves. Entretanto, houve boa concordância entre Rint > 4 cmH2O • L-1 • s-1 e RVA por pletismografia > 2,5 cmH2O • L-1 • s-1 (razão de verossimilhança > 8 e coeficiente kappa = 0,73). CONCLUSÕES: A concordância entre o Rint e a RVA por pletismografia foi boa nos indivíduos menos graves. A concordância para um diagnóstico de aumento da RVA entre os dois métodos também foi forte. A técnica Rint é um método potencialmente útil na prática assistencial em adultos.OBJECTIVE: To determine the agreement between interrupter resistance (Rint) and airway resistance (Raw) by plethysmography in order to verify the clinical applicability of the interrupter technique. METHODS: The Rint technique was performed with the patients in a sitting position, during exhalation, with a nose clip and cheek support. Plethysmography was carried out in accordance with standard protocols. All measurements were taken prior to and after the administration of an inhaled bronchodilator via a metered dose inhaler with a spacer. RESULTS: The study comprised 99 consecutive patients referred to the Porto Alegre Hospital de Clínicas, located in the city of Porto Alegre, Brazil, for pulmonary function testing. Patient ages ranged from 18 to 82 years, and 52 of the patients were women. In the patients with FEV1 > 60% of predicted, there was good agreement between the methods (r = 0.8; intraclass correlation coefficient = 0.8). The Rint values were lower than were those of Raw by plethysmography in the patients with more severe disease. However, there was good agreement between Rint > 4 cmH2O • L-1• s-1 and Raw by plethysmography > 2.5 cmH2O • L-1 • s-1 (likelihood ratio > 8; kappa coefficient = 0.73). CONCLUSIONS: In the patients with less severe disease, there was good agreement between Rint and Raw by plethysmography. The agreement between the two methods was also strong regarding the detection of an increase in Raw. The Rint technique is a potentially useful method for the evaluation of adult patients.

Pollen data collected in Africa at high (Kuruyange, valley swamp, Burundi) and low altitude (Victoria, lake, Uganda; Ngamakala, pond, Congo) showed that after 6 ky before present (BP), pollen of deciduous trees increase their relative percentage, suggesting thus the reduction of the annual amount of precipitation and/or an increase of in the length of the dry season. Until now, pollen-climate transfer functions only investigated mean annual precipitation, due to the absence of modern pollen-assemblage analogs under diversified precipitation regimes. Hence these functions omit the potential effect of a change in precipitation seasonality modifying thus the length of the dry season. In the present study, we use an equilibrium biosphere model (i.e. BIOME3.5) to estimate the sensitivity of equatorial African vegetation, at specific sites, to such changes. Climatic scenarios, differing only in the monthly distribution of the current annual amount of precipitation, are examined at the above three locations in equatorial Africa. Soil characteristics, monthly temperatures and cloudiness are kept constant at their present-day values. Good agreement is shown between model simulations and current biomes assemblages, as inferred from pollen data. To date, the increase of the deciduous forest component in the palaeodata around 6 ky BP has been interpreted as the beginning of a drier climate period. However, our results demonstrate that a change in the seasonal distribution of precipitation could also induce the observed changes in vegetation types. This study confirms the importance of taking into account seasonal changes in the hydrological balance. Palaeoecologists can greatly benefit from the use of dynamic process based vegetation models to acccount for modification of the length of the dry season when they wish to reconstruct vegetation composition or to infer quantitative climate parameters, such as temperature and precipitation, from pollen or vegetation proxy.

Climate and atmospheric CO2 effects on the balance between C3 and C4 plants have received conflicting interpretations based on the analysis of carbon isotopic fractionation (δ13C) in sediments. But, climate and CO2 effects on the C3/C4 balance and δ13C signal are rarely addressed together. Here, we use a process-based model (BIOME4) to disentangle these effects. We simulated the vegetation response to climate and CO2 atmospheric concentration (pCO2) in two sites in which vegetation changed oppositely, with respect to C3 and C4 plants abundance, during the Last Glacial Maximum to Holocene transition. The C3/C4 balance and δ13C signal were primarily sensitive to temperature and CO2 atmospheric partial pressure. The simulated variations were in agreement with patterns observed in palaeorecords. Water limitation favoured C4 plants in case of large negative deviation in rainfall. Although a global parameter, pCO2 affected the δ13C signal differently from one site to the other because of its effects on the C3/C4 balance and on carbon isotopic fractionation in C3 and C4 plants. Simulated Plant functional types (PFT) also differed in their composition and response from one site to the other. The C3/C4 balance involved different competing C3 and C4 PFT, and not homogeneous C3 and C4 poles as often assumed. Process-based vegetation modelling emphasizes the need to account for multiple factors when a palaeo-δ13C signal is used to reconstruct the C3/C4 balance.

Microglia activation and neuroinflammation play a pivotal role in the pathogenesis of lysosomal storage disorders (LSD) affecting the central nervous system (CNS), which are amenable to treatment by hematopoietic stem cell transplantation (HSCT). HSCT efficacy relies on replacing the intra- and extra-vascular hematopoietic cell compartments, including CNS microglia, with a cell population expressing the functional enzyme. Non-invasive and quantitative assessment of microglia activation and of its reduction upon HSCT might allow for evaluation of disease evolution and response to treatment in LSD. We here demonstrate that microglia activation can be quantified ex vivo and in vivo by PET using the peripheral benzodiazepine receptor ligand PK11195 in two models of LSD. Furthermore, we show a differential PBR binding following microglia replacement by donor cells in mice undergoing HSCT. Our data indicates that PBR ligands constitute valuable tools for monitoring the evolution and the response to treatment of LSD with CNS involvement, and enable us to evaluate whether the turnover between endogenous and donor microglia following HSCT could be adequate enough to delay disease progression.

Este artigo trata do item sensível a foco só. Por falta de estudos a seu respeito no português brasileiro (PB), baseamo-nos, sobretudo, no texto de Herburger (2000) Only and even, fazendo adaptações aos nossos dados. Conforme essa autora, uma exigência sintática do only (equivalente ao só no português) é a de que ele tem que ter um elemento focalizado no domínio de seu c-comando – o que para os dados do PB acontece ou em sintaxe visível (a maioria dos casos) ou somente em LF. Atesta-se, ainda, que tal elemento pode ocorrer em qualquer posição sintática e atuar sobre qualquer categoria sintática. Vimos também que a autora assume dois tipos de só, o regular only (só padrão) e o scalar only (só escalar) – análise que será questionada, visando defender um único tipo, a partir de uma semântica sensível ao contexto.

Este artigo investiga os itens de polaridade negativa no Português Brasileiro (PB). A despeito da literatura já robusta sobre polaridade negativa em outras línguas, em particular para o inglês, muito pouco se sabe sobre o tema no PB, tendo talvez como única exceção Ilari (1984), que descreve e analisa locuções negativas. Por isso investigamos se há alguns itens no PB que são itens de polaridade negativa (IPN) e concluímos que ‘sequer’, ‘ainda’, e ‘N algum’ são IPN’s, enquanto o ‘qualquer’, e o ‘o quer seja’ são itens de livre escolha. Investigamos, ainda, sua distribuição e suas condições de licenciamento, discutimos duas abordagens: Ladusaw (2002 [1980]) e Giannakidou (2001), e concluímos que essas não explicam os dados do PB.

The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of natural killer cells, and antibody-dependent cellular cytotoxicity by these cells, as well as phagocytosis by macrophages or neutrophils were inhibited by ibrutinib with a half maximal effective concentration of 0.3–3 μM. Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo. Finally we show that the phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib similarly inhibited the immune cell-mediated mechanisms induced by anti-CD20 antibodies, although the effects of this drug at 10 μM were weaker than those observed with ibrutinib at the same concentration. We conclude that the design of combined treatment schedules of anti-CD20 antibodies with these kinase inhibitors should consider the multiple negative interactions between these two classes of drugs.

Outcome of systemic peripheral T-cell lymphomas (PTCL) is unsatisfactory and no controlled clinical study guides the therapy. Phase II studies suggest to consolidate response achieved after front-line treatment with stem cell transplant (SCT). We retrospectively evaluate the impact of front-line SCT consolidation in a single Center cohort of 209 patients treated during the last two decades. Median age was 49 years (range 15-85) with a prevalence of male sex (61%), advanced stage (68%) while IPI was >2 in 44%. Primary treatment was MACOP-B (39%) CHO(E)P (39%), intensive regimens (18%) or others (4%). Complete response to primary treatment (i.e. before SCT) was 60% (5% partial remission). Forty-four patients further proceeded to SCT while 92 did not receive consolidation. Outcome of primary responders was good, with a 3-year overall survival of 74% (82% in ALCL ALK+ and 69% for the other histologies). By multivariate analysis a better overall survival was significantly associated with IPI

A 56-year-old female with a giant partially thrombosed unruptured carotid-ophthalmic aneurysm was treated with a Pipeline flow diverter. Three months after the procedure, in concomitance with the discontinuation of one of the antiplatelet medications, the patient suffered from a minor stroke and relapsing transient ischemic attacks. The angiography demonstrated the occlusion of the internal carotid artery, and a perfusion-weighted CT scan showed a condition of hypoperfusion. The patient underwent a double-barrel extraintracranial bypass. The postoperative course was uneventful and she has experienced no further ischemic events to date.

Myocardial infarction (MI) is one of the leading causes of death in developed countries and it is characterized by several associated symptomatologies and poor quality of life. Recent data showed a possible interaction between infarction and brain inflammation and activity. Previous studies have demonstrated the beneficial effect of exercise training on deterioration in cardiac function after MI. In this study we analyzed in sedentary and trained rats the microglia and astrocytes 48 hours after MI in PVN, thalamus, prefrontal cortex, and hippocampus through immunofluorescence approach. We found significant changes in specific microglia phenotypes in the brain areas analyzed together with astrocytes activation. Prolonged exercise normalized these morphological changes of microglia and astrocytes in the prefrontal cortex, hippocampus, and thalamus but not in the PVN. Our data suggest that there is an early brain reaction to myocardial infarction induction, involving nonneuronal cells, that is attenuated by the prolonged exercise.

Penetrating injuries to the spine, although less common than motor vehicle accidents and falls, are important causes of injury to the spinal cord. They are essentially of two varieties: gunshot or stab wounds. Gunshot injuries to the spine are more commonly described. Stab wounds are usually inflicted by knife or other sharp objects. Rarer objects causing incidental spinal injuries include glass fragments, wood pieces, chopsticks, nailguns, and injection needles. Just few cases of penetrating vertebral injuries caused by pencil are described. The current case concerns a 42-year-old man with an accidental penetrating stonemason pencil injury into the vertebral canal without neurological deficit. After the self-removal of the foreign object the patient complained of a disabling orthostatic headache. The early identification and treatment of the intracranial hypotension due to the posttraumatic cerebrospinal fluid (CSF) sacral fistulae were mandatory to avoid further neurological complications. In the current literature acute pattern of intracranial hypotension immediately after a penetrating injury of the vertebral column has never been reported.

A natureza das infecções após os transplantes de órgãos sólidos mudou, significativamente, com o advento de potentes esquemas imunossupressores, o uso rotineiro de profilaxia antimicrobiana e os avanços das técnicas de diagnóstico microbiológico. Novos patógenos estão sendo identificados nessa população, incluindo vários com significante perfil de resistência a antimicrobianos. Cada tipo de enxerto apresenta riscos de infecções particulares, sendo os transplantes de intestino e multivisceral importantes exemplos disso. Entretanto, os padrões gerais de infecção são similares a todos os transplantes de órgãos sólidos. As infecções nessas situações podem ser divididas em categorias: relacionadas ao doador, relacionadas ao receptor, infecções adquiridas na comunidade e infecções relacionadas à assistência à saúde. A cronologia das infecções após transplante é determinada pela natureza e intensidade das exposições epidemiológicas individuais e do estado de equilíbrio da imunossupressão. A escassez de estudos epidemiológicos das infecções pós-transplantes de intestino e multivisceral ainda mantêm sua compreensão, mais no estado da arte do que como ciência. O objetivo deste estudo é descrever os dados epidemiológicos das infecções fúngicas pós-transplantes de intestino e multivisceral. Os agentes mais prevalentes nos transplantes de intestino e multivisceral foram: Candida spp. e Aspergillus spp. Os principais sítios de infecção foram: sítio cirúrgico, intra-abdominal, corrente sanguínea, cateter venoso central, urinário e respiratório. Os fatores de risco identificados foram: rejeição aguda, dose alta de imunossupressão, uso de dispositivos invasivos, cirurgias extensas e reoperação, enxerto contaminado, infecção prévia e paciente hospitalizado no período pré-transplante.

Objectives. To evaluate the influence of dentine on the pH of different medications in standardized simulated canals. Materials and Methods. Forty resin blocks were divided into groups with and without dentine powder, as follows: 2% chlorhexidine gel; 2% chlorhexidine gel associated with calcium hydroxide PA; calcium hydroxide PA delivered in propylene glycol 600; and NPG delivered in distilled water. The dentine powder was obtained from the root dentine of bovine teeth and added to the medications. The simulated canals were placed in containers with 1.5 mL of deionized water and pH was monitored in multiple intervals, up to 30 days. The mean pH values were calculated and submitted to statistical analysis using paired Student’s t-test and ANOVA complemented by the Tukey test (p0.05). The pH values of calcium hydroxide were significantly higher than those of NPG in the first 24 hours (p

Occlusion of the intracranial internal carotid artery (ICA) by a pituitary adenoma with resulting cerebral ischemia is a very rare but devastating occurrence. The authors present a case in which a condition of symptomatic ICA occlusion due to a giant pituitary adenoma was successfully treated using a preliminary extraintracranial bypass as a “bridge” to the tumor removal. A 52-year-old patient presented with a minor stroke followed by pressure-dependent transient ischemic attacks consistent with a condition of hypoperfusion. MR imaging and a digital subtraction angiography revealed a pituitary adenoma occluding the ICA on the right side. He underwent a superficial temporal artery to middle cerebral artery (STA-MCA) bypass with the aim of revascularizing the ischemic hemisphere and reducing the risk of perioperative stroke or stroke evolution. The patient was subsequently operated on to remove the adenoma through a transsphenoidal approach. The postoperative course was uneventful and the patient has suffered no further ischemic events. When there are no emergency indications to decompress the optical pathways but the patient is at risk of impending stroke because of ICA occlusion, a two-step strategy consisting of a bypass and subsequent removal of the pituitary adenoma may be a valuable option.

Se abordó el tema de maltrato infantil, la estabilidad emocional y el bienestar físico de los infantes. Se analizó el concepto de la paternidad positiva como una propuesta de modelo educativo para padres orientado al desarrollo y al vínculo de la familia con la sociedad. El trabajo se propone analizar cómo la paternidad positiva influye efectivamente en el desarrollo infantil.

Aneurysmal bone cyst is a pseudotumoral lesion. Complete resection prior to selective arterial embolization seems to be the treatment of choice for the more extensive and destructive lesions. In these cases maintaining stability of the cervical spine is critical. This can be very challenging in children and adolescents in whom the axial skeleton is still growing. In this case a young girl presented with a voluminous cervical aneurysmal bone cyst encaging both vertebral arteries and spinal cord. The lesion was treated with aggressive surgical resection, followed by cervical vertebral fusion with instrumentation. After nine months the patient referred no pain and no neurological deficit. MRI scans showed an extensive local recurrence. The family of the young girl refused any other therapy and any other followup. The patients returned to our attention after five years with no pain and neurological deficit. Cervical spine radiographs and MRI scans showed a complete regression of the extensive local recurrence. In the literature, the possibility of spontaneous regression of residual part or local recurrence is reported. The case of this young girl provided the chance to attend a spontaneous regression in an extensive recurrence of aneurismal bone cyst.

BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p

Despite the refinement of the cognitive treatment for eating disorders, relatively high dropout rates represent a major problem for therapists and researchers. This study investigated the case of a patient with a diagnosis of bulimia nervosa, who dropped out of outpatient CBT after 28 weekly sessions. In addition to standard clinical outcome assessment, we examined how patient's psychological functioning and therapeutic alliance changed across sessions by applying observer-rating scales to the therapy transcripts. Although the patient reported some improvement at the six-month retest, observer ratings showed persistence of impaired functioning and frequent ruptures in the patient-therapist relationship throughout the treatment. We concluded that a thorough examination of the therapy process might help to understand the factors that lead to premature treatment termination.

Candida osteomyelitis in the current literature is an emerging infection. The factors contributing to its emergence include a growing population of immunosuppressed patients, invasive surgeries, broad-spectrum antibiotics, injection drug users, and alcohol abuse. The diagnosis requires a high degree of suspicion. The insidious progression of infection and the nonspecificity of laboratory and radiologic findings may contribute to a delay in diagnosis. The current case concerns a 27-year-old man with a spinal cord injury who, after undergoing anterior cervical fixation and fusion surgery, developed postoperative systemic bacterial infection and required long-term antibiotic therapy. After six months, a CT scan demonstrated an almost complete anterior dislocation of the implants caused by massive bone destruction and reabsorption in Candida albicans infection. The patient underwent a second intervention consisting firstly of a posterior approach with C4–C7 fixation and fusion, followed by a second anterior approach with a corpectomy of C5 and C6, a tricortical bone grafting from the iliac crest, and C4–C7 plating. The antifungal therapy with fluconazole was effective without surgical debridement of the bone graft, despite the fact that signs of the bone graft being infected were seen from the first cervical CT scans carried out after one month.