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Purpose of the article: The aim of this multicenter observational study is to report data from real world on the use of bimekizumab in patients aged ≥ 65 years with moderate-to-severe plaque psoriasis. Elderly patients are poorly represented in clinical trials on bimekizumab for plaque psoriasis, and real-world studies are important to guide clinical choices.Materials and methods: A retrospective multicenter study was conducted in 33 dermatological outpatient clinics in Italy. Patients aged ≥ 65 years, with moderate-to-severe plaque psoriasis and treated with bimekizumab were enrolled. No exclusion criteria were applied. Bimekizumab was administered following the Italian Guidelines for the management of plaque psoriasis and according to the summary of product characteristics, in adult patients who were candidates for systemic treatments. Overall, 98 subjects were included, and received bimekizumab up to week 36. Clinical and demographic data were collected before the initiation of treatment with bimekizumab. At baseline and each dermatological examination (4, 16, and 36 weeks), clinical outcomes were measured by the following parameters: (1) PASI score; (2) site-specific (scalp, palmoplantar, genital, nail) Psoriasis Global Assessment (PGA). At each visit, the occurrence of any adverse events (AEs) was recorded, including serious AEs and AEs leading to bimekizumab discontinuation.Results: The mean PASI score was 16.6 ± 9.4 at baseline and significantly decreased to 4.3 ± 5.2 after 4 weeks (p < 0.001), and 1.1 ± 1.7 after 16 week (p < 0.001). This level of improvement was maintained after 36 weeks (p < 0.001). PASI ≤2 was recorded in 36 (36.7%) at week 4, 68% and 69.4% at week 16 and 36, respectively. By week 16, 86/98 (87.8%) patients reached PASI75, 71/98 (72.4%) obtained PASI90, and 52/98 (53.1%) PASI100. Binary logistic regression tests showed a significant association of PASI100 by week 4 with lower PASI at baseline. PASI 100 at 16 or 36 weeks was not associated with baseline PASI, obesity, age, gender, previously naïve state, and presence of psoriatic arthritis. Patients naïve to biologics at baseline had similar response to bimekizumab as non-naïve subjects.Conclusions: Bimekizumab is a suitable option for elder patients as it is effective, tolerated and has a convenient schedule.
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Psoríase , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Psoríase/patologia , Estudos Retrospectivos , Masculino , Idoso , Feminino , Itália , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Idoso de 80 Anos ou maisRESUMO
Atopic dermatitis (AD) is a chronic inflammatory disease that may involve any cutaneous site; involvement of the genital area may greatly impair patients' quality of life but, as the inspection of genitals is not usually conducted during the routine physical examination of patients with AD, the genital presentation of AD is frequently neglected and under-reported. We decided to evaluate the incidence of genital AD in patients with moderate-severe AD and the relative response to anti-interleukin (IL)-4/IL-13 dupilumab. In our study, a high incidence of genital AD emerged but the use of dupilumab allowed a generalized improvement.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Fármacos Dermatológicos/uso terapêutico , Genitália Feminina/patologia , Genitália Masculina/patologia , Subunidade alfa de Receptor de Interleucina-4/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Optical forces are used to push and aggregate gold nanorods onto several substrates creating surface-enhanced Raman scattering (SERS) active hot spots for Raman-based identification of proteins. By monitoring the increase of the protein SERS signal, we observe different aggregation times for different curvatures of the substrates. The slower aggregation dynamics on curved surfaces is justified by a simple geometrical model. In particular, this technique is used to decorate three-dimensional microstructures and to quickly realize hybrid micro/nanosensors for highly sensitive detection of biological material directly in a liquid environment.
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Abstract Heavy-ion induced two-neutron transfer reactions (18O,16O) at 84 MeV were studied on several targets up to high excitation energy of the residual nucleus thanks to the use of the MAGNEX magnetic spectrometer to detect the ejectiles. The obtained results indicate of the important role played by the nuclear paring.
Resumen Se estudiaron reacciones de transferencia de dos neutrones inducidas por iones pesados (18O, 16O) a 84 MeV en varios blancos hasta una alta energía de excitación del núcleo residual gracias al uso del espectrómetro magnético MAGNEX para detectar los residuos eyectados. Los resultados obtenidos indican el importante papel desempeñado por el apareamiento nuclear.
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Abstract NUMEN proposes cross sections measurements of Heavy-Ion double charge exchange reactions as an innovative tool to access the nuclear matrix elements, entering the expression of the life time of Neutrinoless double beta decay (0νββ). A key aspect of the projectis the use at INFN-Laboratori Nazionali del Sud (LNS) of the Superconducting Cyclotron (CS) for the acceleration of the required high resolution and low emittance heavy-ion beams and of MAGNEX large acceptance magnetic spectrometer for the detection of the ejectiles. The experimental measurements of double charge exchange reactions induced by heavy ions present a number of challenging aspects, since such reactions are characterized by very low cross sections. First experimental results give encouraging indication on the capability to access quantitative information towards the determination of the Nuclear Matrix Elements for 0νββ decay.
Resumen NUMEN propone mediciones de secciones eficaces de reacciones de intercambio de carga doble de iones pesados como una herramienta innovadora para acceder a los elementos de la matriz nuclear, entrando en la expresión del tiempo de vida de la desintegración beta doble sin neutrino (0νββ). Un aspecto clave del proyecto es el uso en INFN-Laboratori Nazionali del Sud (LNS) del ciclotrón superconductor (CS) para la aceleración de los haces de iones pesados de alta resolución y baja emitancia requeridos y del espectrómetro magnético de gran aceptación MAGNEX para la detección de los residuos eyectados. Las mediciones experimentales de reacciones de intercambio de carga doble inducidas por iones pesados presentan una serie de aspectos desafiantes, ya que tales reacciones se caracterizan por secciones eficaces muy bajas. Los primeros resultados experimentales dan una indicación alentadora sobre la capacidad de acceder a información cuantitativa para la determinación de los Elementos de la Matriz Nuclear para la descomposición de 0νββ.
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In recent years, considerable effort has been devoted to the synthesis and characterization of two-dimensional materials. Liquid phase exfoliation (LPE) represents a simple, large-scale method to exfoliate layered materials down to mono- and few-layer flakes. In this context, the contactless trapping, characterization, and manipulation of individual nanosheets hold perspectives for increased accuracy in flake metrology and the assembly of novel functional materials. Here, we use optical forces for high-resolution structural characterization and precise mechanical positioning of nanosheets of hexagonal boron nitride, molybdenum disulfide, and tungsten disulfide obtained by LPE. Weakly optically absorbing nanosheets of boron nitride are trapped in optical tweezers. The analysis of the thermal fluctuations allows a direct measurement of optical forces and the mean flake size in a liquid environment. Measured optical trapping constants are compared with T-matrix light scattering calculations to show a quadratic size scaling for small size, as expected for a bidimensional system. In contrast, strongly absorbing nanosheets of molybdenum disulfide and tungsten disulfide are not stably trapped due to the dominance of radiation pressure over the optical trapping force. Thus, optical forces are used to pattern a substrate by selectively depositing nanosheets in short times (minutes) and without any preparation of the surface. This study will be useful for improving ink-jet printing and for a better engineering of optoelectronic devices based on two-dimensional materials.
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This Letter reports a study of the highly debated ^{10}Li structure through the d(^{9}Li,p)^{10}Li one-neutron transfer reaction at 100 MeV. The ^{10}Li energy spectrum is measured up to 4.6 MeV and angular distributions corresponding to different excitation energy regions are reported for the first time. The comparison between data and theoretical predictions, including pairing correlation effects, shows the existence of a p_{1/2} resonance at 0.45±0.03 MeV excitation energy, while no evidence for a significant s-wave contribution close to the threshold energy is observed. Moreover, two high-lying structures are populated at 1.5 and 2.9 MeV. The corresponding angular distributions suggest a significant s_{1/2} partial-wave contribution for the 1.5 MeV structure and a mixing of configurations at higher energy, with the d_{5/2} partial-wave contributing the most to the cross section.
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Optical trapping of silver nanoplatelets obtained with a simple room temperature chemical synthesis technique is reported. Trap spring constants are measured for platelets with different diameters to investigate the size-scaling behaviour. Experimental data are compared with models of optical forces based on the dipole approximation and on electromagnetic scattering within a T-matrix framework. Finally, we discuss applications of these nanoplatelets for surface-enhanced Raman spectroscopy.
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Giant resonances are collective excitation modes for many-body systems of fermions governed by a mean field, such as the atomic nuclei. The microscopic origin of such modes is the coherence among elementary particle-hole excitations, where a particle is promoted from an occupied state below the Fermi level (hole) to an empty one above the Fermi level (particle). The same coherence is also predicted for the particle-particle and the hole-hole excitations, because of the basic quantum symmetry between particles and holes. In nuclear physics, the giant modes have been widely reported for the particle-hole sector but, despite several attempts, there is no precedent in the particle-particle and hole-hole ones, thus making questionable the aforementioned symmetry assumption. Here we provide experimental indications of the Giant Pairing Vibration, which is the leading particle-particle giant mode. An immediate implication of it is the validation of the particle-hole symmetry.
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The macrobenthic community was compared at four sites characterized by varying degrees of freshwater input, organic enrichment and confinement in the Cabras lagoon (Sardinia, Italy). Three sites, riverine (C1), confined (C2) and seaward (C3), were studied on two dates of summer 2010 and on two dates of winter 2011. A fourth site (C12), representative of the central sector of the Cabras lagoon, was included in this study using the extensive historical datasets at our disposal from previously published work. We aimed to test the hypothesis that (1) the benthos is distributed according to the recently proposed concept of habitat saprobity for coastal lagoons that unifies the Pearson-Rosenberg (sensu organic enrichment) and Guélorget-Perthuisot (sensu confinement) models, and (2) indicator species of different saprobic levels can be identified among dominant species occurring along the saprobity gradient. Salinity was also considered as an additional agent of selection in brackish environments. Irrespective of significant seasonal changes within each site, our results highlighted major environmental and biotic differences between sites. At the northward riverine site (C1), most affected by freshwater input and with limited organic matter (OM) enrichment, Corophium orientale was the single dominant species. The most confined site (C2) was characterized by the highest levels of sedimentary OM and benthic Chlorophyll-a and by mesohaline conditions; the site was inhabited mainly by the halolimnobic Hediste diversicolor and Hydrobia spp. Site C12, characterized by a high OM load and high residence time, was dominated by the opportunistic detritivorous Alitta succinea and Polydora ciliata. At the southernmost seaward site (C3) the considerable seawater renewal, resulting in high salinity (only in summer) and limited OM load, favored a much more diverse macrobenthic assemblage, essentially composed of both marine species, such as Corophium insidiosum, Gammarus aequicauda, and brackish-water species, such as Lekanesphaera hookeri and Idotea chelipes. We conclude that the biotic and abiotic characteristics of the Cabras lagoon can be represented by a succession of spatial zones along two main gradients determined by salinity and saprobity. The salinity gradient proved to be the main structural feature in the oligohaline pole, while in the range of variable salinity, saprobity appeared to be the main selection factor. To illustrate our findings, we provide a graphical representation summarizing the changes in environmental parameters and indicator species along the salinity and saprobity gradients.
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Distribuição Animal , Biota , Poluição Ambiental/análise , Estuários , Invertebrados/fisiologia , Modelos Biológicos , Animais , Sedimentos Geológicos , Itália , Mar Mediterrâneo , Salinidade , Especificidade da EspécieRESUMO
We have previously carried out two genome-wide scans in samples of Finns ascertained for schizophrenia from national epidemiological registers. Here, we report data from a third genome scan in a nationwide Finnish schizophrenia study sample of 238 pedigrees with 591 affected individuals. Of the 238 pedigrees, 53 originated from a small internal isolate (IS) on the eastern border of Finland with a well established genealogical history and a small number of founders, who settled in the community 300 years ago. The total study sample of over 1200 individuals were genotyped, using 315 markers. In addition to the previously identified chromosome 1 locus, two new loci were identified on chromosomes 2q and 5q. The highest LOD scores were found in the IS families with marker D2S427 (Z(max) = 4.43) and in the families originating from the late settlement region with marker D5S414 (Z(max) = 3.56). In addition to 1q, 2q and 5q, some evidence for linkage emerged at 4q, 9q and Xp, the regions also suggested by our previous genome scans, whereas, in the nationwide study sample, the region at 7q failed to show further evidence of linkage. The chromosome 5q finding is of particular interest, since several other studies have also shown evidence for linkage in the vicinity of this locus.
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Cromossomos Humanos Par 2 , Cromossomos Humanos Par 5 , Esquizofrenia/genética , Cromossomos Humanos Par 1 , Finlândia , Ligação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Repetições de Microssatélites , Linhagem , Estatísticas não ParamétricasRESUMO
PURPOSE: To evaluate the efficacy of hepatic enhancement characteristics for identification of patients with breast cancer who are at risk for future hepatic metastases. MATERIALS AND METHODS: Triple-phase helical computed tomography (CT) was performed in 60 patients with known breast cancer without visible hepatic metastases. Peak hepatic attenuation and enhancement, and attenuation and enhancement at 25 and 30 seconds were obtained. Ratios of hepatic attenuation or enhancement at 25 and 30 seconds to peak hepatic attenuation or enhancement were calculated. A Wilcoxon rank sum test was used to compare patients with and those without subsequent hepatic metastases. RESULTS: During a mean 18-month follow-up, 18 patients (30%) developed hepatic metastases. Decreases in peak hepatic attenuation and enhancement and increases in hepatic attenuation and enhancement ratios at 25 and 30 seconds were seen in patients who developed metastases compared with those who did not (P < .05). When corrected for chemotherapy interval, these differences were not statistically significant. Using a threshold value of 0.40 or more for the enhancement ratio at 30 seconds resulted in sensitivity of 28%, specificity of 92%, and accuracy of 55%. CONCLUSION: Patients with breast cancer who develop subsequent hepatic metastases have higher relative hepatic arterial perfusion during triple-phase CT; however, after correction for chemotherapy interval, this difference was not statistically significant. Threshold values cannot be used reliably to identify patients who will develop metastases.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Neoplasias da Mama/irrigação sanguínea , Meios de Contraste , Feminino , Seguimentos , Humanos , Iopamidol , Fígado/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Intensificação de Imagem Radiográfica , Fluxo Sanguíneo Regional/fisiologiaRESUMO
The aim of this paper was to examine the indications and limits of pre- and intra-operative instrumental diagnosis of gastric cancer. In order to achieve this effectively, the authors emphasized the importance of proper staging methods and obtained a detailed description of tumor diffusion. The most important diagnostic instruments considered were magnetic resonance, endosonography, intra-operative echography, pre- and intra-operative immunoscintography and a cytological examination of peritoneal lavage fluid. The authors concluded that pre- and intra-operative staging of gastric cancer is important for two major reasons: it results in the most accurate definition possible of disease evolution, enabling a proper therapeutic program; and it involves a combination of three complementary metasurgical treatments.
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Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Citodiagnóstico , Gastroscopia , Humanos , Período Intraoperatório , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Prognóstico , Sensibilidade e Especificidade , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
A series of 8 patients with spontaneous rupture of the esophagus is analysed. Correct diagnosis is difficult. The time lapse between the rupture and diagnosis nevertheless seems to be the most important single factor in the outlook for treatment of spontaneous rupture of the esophagus. Early primary closure of the tear and good drainage of the mediastinum and pleural cavity give the best results in such cases. Sometimes a conservative management should be advocated for the treatment of esophageal perforations.
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Doenças do Esôfago , Doenças do Esôfago/diagnóstico , Doenças do Esôfago/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea , Síndrome , Fatores de TempoRESUMO
Cortical functions concerned with the execution of skilled movements can be studied through complex interactive tasks. Skilled performance task (SPT) offers the greatest deal of information about the electrophysiological components reflecting pre-programming, execution of the movement and control of the results. Overall, these components are indicated as "movement-related brain macropotentials' (MRBMs). Among them, Bereitschaftspotential (BP) reflects cerebral processes related to the preparation of movement and skilled performance positivity (SPP) reflects control processes on the result of performance. There is some evidence supporting a training effect on MRBMs, but less clear is whether long-term practice of a skilled activity could modify learning strategies of a new skilled task. We recorded MRBMs in subjects trained for a long time to perform a highly skillful athletic activity, i.e. gun shooting, and in a group of control subjects without any former experience in skilled motor activities. Our findings demonstrated the existence of a relationship between pre-programming and performance control, as suggested by decrease of BP amplitude and increase of SPP amplitude in presence of high levels of performance. Long-term practice seems to develop better control models on performance, that reduce the need of a high mental effort in pre-programming a skilled action.
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Variação Contingente Negativa/fisiologia , Aprendizagem/fisiologia , Adulto , Eletroencefalografia , Humanos , Masculino , Tempo de Reação/fisiologia , Fatores de TempoRESUMO
A patient with typical Ph1-positive CML was studied during sequential phases: (1) initial chronic phase, (2) first myeloid blast crisis, (3) second chronic phase, and (4) accelerated disease leading to a second blast crisis. A point mutation in codon 239 of the p53 gene and a novel chromosome 17 alteration appeared concomitantly with the first blast crisis and then disappeared with re-establishment of a second chronic phase. They did not reappear with the second acute phase, indicating that the clone responsible for the original blast crisis had been suppressed and supplanted by another clone of malignant cells. This observation suggests that in at least some CML patients drug therapy can suppress or eliminate an aggressive malignant cell clone, but that the underlying molecular defect in haemopoietic cells (in this case the c-ABL translocation) persists and other aggressive clones with different molecular lesions eventually arise. Our observations and inferences are consistent with the hypothesis advanced by Fialkow et al (1991) to explain clonal remissions in acute non-lymphocytic leukaemia.
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Crise Blástica/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação Puntual , Adulto , Sequência de Bases , Células Clonais , Éxons , Genes p53/genética , Humanos , Dados de Sequência Molecular , RecidivaRESUMO
Chronic myelocytic or Ph1-positive acute lymphoblastic leukemias have been analyzed for alterations in a variety of proto-oncogenes and anti-oncogenes implicated in the progression of chronic myeloid leukemia (CML) from its chronic phase to blast crisis. The most frequent genetic change found in disease evolution is an alteration of the p53 gene involving a point mutation, a rearrangement or a deletion. These gene changes are common in myeloid and undifferentiated variants of blast crisis but are usually undetectable in lymphoid leukemic transformants. Other molecular changes also occur in the clonal evolution of CML. The retinoblastoma-susceptibility (Rb) gene is an anti-oncogene. Structural abnormalities of Rb are frequent in all types of human acute leukemia, but are particularly common in Ph1-positive leukemia of lymphoid phenotype including both Ph1-positive ALL and lymphoid blast crisis of CML. Changes in Rb occur early in the transition to blast crisis with loss of Rb protein being the common factor. Mutations in the N-RAS gene also occur, but are rare in typical blast crisis. They are sometimes seen in Ph1-negative myeloid blast crisis. Since changes in the p53 gene are generally associated with progression of disease of a myeloid phenotype and changes in the Rb gene occur more often with a lymphoid phenotype, a particular molecular alteration may influence the character of disease evolution in CML.
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Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Crise Blástica , Genes do Retinoblastoma , Genes p53 , Genes ras , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , MutaçãoRESUMO
The retinoblastoma-susceptibility (Rb) gene is an antioncogene that is frequently altered in retinoblastomas, sarcomas, and some epithelial tumors. We examined the structure of the Rb gene by Southern blotting in 215 cases of leukemias and lymphomas of diverse phenotype and in 15 leukemic cell lines. In selected cases Rb protein expression was examined with specific monoclonal antibodies. Structural abnormalities of the Rb gene with absent protein expression were frequent in all types of human acute leukemia, but were particularly common (27% incidence) in M4 and M5 myeloid leukemia with monocytic differentiation and in Philadelphia chromosome (Ph1)-positive leukemia of lymphoid phenotype (11% to 29% incidence). Changes in Rb were observed early in the transition to acute leukemia in cases of myelodysplastic syndrome and in the accelerated phase of chronic myelocytic leukemia in transition to blast crisis. In one case, molecular changes in Rb could be correlated with leukemia remission and relapse. We conclude that the Rb antioncogene is commonly involved in the evolution of human acute leukemias, particularly in those of a monocytic phenotype and in lymphoid leukemia in which there is an antecedent alteration of the Ph1 chromosome.