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2.
Artigo em Inglês | MEDLINE | ID: mdl-32332918

RESUMO

We conducted a phase I-II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria.

3.
Sci Adv ; 5(9): eaaw3492, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31517044

RESUMO

European populations display low genetic differentiation as the result of long-term blending of their ancient founding ancestries. However, it is unclear how the combination of ancient ancestries related to early foragers, Neolithic farmers, and Bronze Age nomadic pastoralists can explain the distribution of genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the continental diversity, but have been systematically understudied. Here, we characterize the ancestry profiles of Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe, and the rest of the world. Italian genomes capture several ancient signatures, including a non-steppe contribution derived ultimately from the Caucasus. Differences in ancestry composition, as the result of migration and admixture, have generated in Italy the largest degree of population structure detected so far in the continent, as well as shaping the amount of Neanderthal DNA in modern-day populations.


Assuntos
DNA Antigo , Bases de Dados Genéticas , Grupo com Ancestrais do Continente Europeu/genética , Deriva Genética , Genoma Humano , Animais , Estudo de Associação Genômica Ampla , História Antiga , Genética Humana , Humanos , Itália , Homem de Neandertal/genética
4.
J Neural Eng ; 16(2): 026037, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30754028

RESUMO

OBJECTIVE: Maintaining upright posture is a complex task governed by the integration of afferent sensorimotor and visual information with compensatory neuromuscular reactions. The objective of the present work was to characterize the visual dependency and functional dynamics of cortical activation during postural control. APPROACH: Proprioceptic vibratory stimulation of calf muscles at 85 Hz was performed to evoke postural perturbation in open-eye (OE) and closed-eye (CE) experimental trials, with pseudorandom binary stimulation phases divided into four segments of 16 stimuli. 64-channel EEG was recorded at 512 Hz, with perturbation epochs defined using bipolar electrodes placed proximal to each vibrator. Power spectra variation and linearity analysis was performed via fast Fourier transformation into six frequency bands (Δ, 0.5-3.5 Hz; θ, 3.5-7.5 Hz; α, 7.5-12.5 Hz; ß, 12.5-30 Hz; [Formula: see text], 30-50 Hz; and [Formula: see text], 50-80 Hz). Finally, functional connectivity assessment was explored via network segregation and integration analyses. MAIN RESULTS: Spectra variation showed waveform and vision-dependent activation within cortical regions specific to both postural adaptation and habituation. Generalized spectral variation yielded significant shifts from low to high frequencies in CE adaptation trials, with overall activity suppressed in habituation; OE trials showed the opposite phenomenon, with both adaptation and habituation yielding increases in spectral power. Finally, our analysis of functional dynamics reveals novel cortical networks implicated in postural control using EEG source-space brain networks. In particular, our reported significant increase in local θ connectivity may signify the planning of corrective steps and/or the analysis of falling consequences, while α band network integration results reflect an inhibition of error detection within the cingulate cortex, likely due to habituation. SIGNIFICANCE: Our findings principally suggest that specific cortical waveforms are dependent upon the availability of visual feedback, and we furthermore present the first evidence that local and global brain networks undergo characteristic modification during postural control.

5.
Science ; 361(6404): 774-777, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-29976795

RESUMO

Jupiter's aurorae are produced in its upper atmosphere when incoming high-energy electrons precipitate along the planet's magnetic field lines. A northern and a southern main auroral oval are visible, surrounded by small emission features associated with the Galilean moons. We present infrared observations, obtained with the Juno spacecraft, showing that in the case of Io, this emission exhibits a swirling pattern that is similar in appearance to a von Kármán vortex street. Well downstream of the main auroral spots, the extended tail is split in two. Both of Ganymede's footprints also appear as a pair of emission features, which may provide a remote measure of Ganymede's magnetosphere. These features suggest that the magnetohydrodynamic interaction between Jupiter and its moon is more complex than previously anticipated.

6.
Nature ; 555(7695): 216-219, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29516997

RESUMO

The familiar axisymmetric zones and belts that characterize Jupiter's weather system at lower latitudes give way to pervasive cyclonic activity at higher latitudes. Two-dimensional turbulence in combination with the Coriolis ß-effect (that is, the large meridionally varying Coriolis force on the giant planets of the Solar System) produces alternating zonal flows. The zonal flows weaken with rising latitude so that a transition between equatorial jets and polar turbulence on Jupiter can occur. Simulations with shallow-water models of giant planets support this transition by producing both alternating flows near the equator and circumpolar cyclones near the poles. Jovian polar regions are not visible from Earth owing to Jupiter's low axial tilt, and were poorly characterized by previous missions because the trajectories of these missions did not venture far from Jupiter's equatorial plane. Here we report that visible and infrared images obtained from above each pole by the Juno spacecraft during its first five orbits reveal persistent polygonal patterns of large cyclones. In the north, eight circumpolar cyclones are observed about a single polar cyclone; in the south, one polar cyclone is encircled by five circumpolar cyclones. Cyclonic circulation is established via time-lapse imagery obtained over intervals ranging from 20 minutes to 4 hours. Although migration of cyclones towards the pole might be expected as a consequence of the Coriolis ß-effect, by which cyclonic vortices naturally drift towards the rotational pole, the configuration of the cyclones is without precedent on other planets (including Saturn's polar hexagonal features). The manner in which the cyclones persist without merging and the process by which they evolve to their current configuration are unknown.

7.
Bone Marrow Transplant ; 53(1): 58-63, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29084200

RESUMO

Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current 'real life' situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.


Assuntos
Doença Enxerto-Hospedeiro/terapia , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Itália , Masculino
9.
Bone Marrow Transplant ; 52(2): 238-244, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27643865

RESUMO

This study evaluated the safety and efficacy of thiotepa-based regimens before allogeneic stem cell transplantation in 310 adult patients with AML. Disease status at the time of transplantation was CR1 in 50%, CR2+ in 23.5% and advanced disease in 26.5%. Transplantation was performed from haploidentical (35%), matched sibling (27%), unrelated (20%) or cord blood (18%) donors. As for safety: mucositis occurred in 46.8% of the patients and the cumulative incidence (CI) of sinusoidal obstruction syndrome was 4.0%. With a median follow-up of 37 months, the CI of acute GvHD grade>II was 26.5%, whereas CI of chronic GvHD was 28.1% at 3 years. CI for non-relapse mortality at 3 years was 38.4%, 49.7% and 45.4% for patients in CR1, CR2+ and advanced disease, respectively (P=0.10). Relapse incidence at 3 years was 20.2, 30.7 and 40.6% in these three respective groups (P=0.002). CI for 3-year leukemia-free survival and overall survival were 41.4% and 45.6% (CR1), 19.6% and 27.7% (CR2+), and 13.9% and 13.6% (advanced disease), respectively (P<10-4 for both). Our data suggest that thiotepa-based conditioning therapy in AML is feasible, effective and safe, as investigated for sinusoidal obstruction syndrome and mucositis.


Assuntos
Leucemia Mieloide Aguda , Transplante de Células-Tronco , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mucosite/mortalidade , Mucosite/prevenção & controle , Recidiva , Taxa de Sobrevida
11.
Anal Chim Acta ; 933: 50-8, 2016 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-27496996

RESUMO

In this work, a comparative study of two novel algorithms to perform sample selection in local regression based on Partial Least Squares Regression (PLS) is presented. These methodologies were applied for Near Infrared Spectroscopy (NIRS) quantification of five major constituents in corn seeds and are compared and contrasted with global PLS calibrations. Validation results show a significant improvement in the prediction quality when local models implemented by the proposed algorithms are applied to large data bases.


Assuntos
Algoritmos , Sementes/química , Zea mays/química , Análise dos Mínimos Quadrados , Modelos Lineares , Espectroscopia de Luz Próxima ao Infravermelho
12.
J Chromatogr A ; 1467: 255-260, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27291863

RESUMO

In this work, we studied the combination of chemometric methods with chromatographic separations as a strategy applied to the analysis of enantiomers when complete enantioseparation is difficult or requires long analysis times and, in addition, the target signals have interference from the matrix. We present the determination of ibuprofen enantiomers in pharmaceutical formulations containing homatropine as interference by chiral HPLC-DAD detection in combination with partial least-squares algorithms. The method has been applied to samples containing enantiomeric ratios from 95:5 to 99.5:0.5 and coelution of interferents. The results were validated using univariate calibration and without homatropine. Relative error of the method was less than 4.0%, for both enantiomers. Limits of detection (LOD) and quantification (LOQ) for (S)-(+)-ibuprofen were 4.96×10-10 and 1.50×10-9mol, respectively. LOD and LOQ for the R-(-)-ibuprofen were LOD=1.60×10-11mol and LOQ=4.85×10-11mol, respectively. Finally, the chemometric method was applied to the determination of enantiomeric purity of commercial pharmaceuticals. The ultimate goal of this research was the development of rapid, reliable, and robust methods for assessing enantiomeric purity by conventional diode array detector assisted by chemometric tools.


Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão , Ibuprofeno/análise , Ibuprofeno/química , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/normas , Tropanos/química , Algoritmos , Calibragem , Combinação de Medicamentos , Análise dos Mínimos Quadrados , Limite de Detecção , Preparações Farmacêuticas/química , Reprodutibilidade dos Testes , Estereoisomerismo
13.
Bone Marrow Transplant ; 51(8): 1032-40, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27042841

RESUMO

Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT) worldwide. The safety and efficacy of reducing hospital stay for MM patients undergoing ASCT have been widely explored, and different outpatient models have been proposed. However, there is no agreement on the criteria for selecting patients eligible for this strategy as well as the standards for their clinical management. On the basis of this rationale, the Italian Group for Stem Cell Transplantation (GITMO) endorsed a project to develop guidelines for the management of outpatient ASCT in MM, using evidence-based knowledge and consensus-formation techniques. An expert panel convened to discuss the currently available data on the practice of outpatient ASCT management and formulated recommendations according to the supporting evidence. Evidence gaps were filled with consensus-based statements. Three main topics were addressed: (1) the identification of criteria for selecting MM patients eligible for outpatient ASCT management; (2) the definition of standard procedures for performing outpatient ASCT (model, supportive care and monitoring during the aplastic phase); (3) the definition of the standard criteria and procedures for re-hospitalization during the aplastic phase at home. Herein, we report the summary and the results of the discussion and the consensus.


Assuntos
Consenso , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Pacientes Ambulatoriais , Guias de Prática Clínica como Assunto/normas , Transplante Autólogo , Protocolos Clínicos/normas , Conferências de Consenso como Assunto , Hospitalização , Humanos , Itália , Seleção de Pacientes
14.
Eur J Paediatr Dent ; 17(1): 36-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26949237

RESUMO

AIM: Studies on prevalence of malocclusion support the planning and provision of public dental services. The aim of the study was to assess the prevalence of malocclusion and occlusal traits in adolescents aged 14 years from public secondary schools in the area of Health District n.15 - Veneto region, Italy. STUDY DESIGN: Cross-sectional survey. METHODS: Out of a randomly selected sample of 1187 subjects, 444 adolescents (55% males, 45% females) were evaluated in the school settings according to the criteria adopted by Brunelle et al. [1996]. Alginate impressions were then taken for 380 students together with a wax bite. The occlusal traits of the cast were analysed and IOTN was established. RESULTS: The most common occlusal traits measured on casts were overjet >3 mm (48%), overbite >3 mm (39%), midline misalignment (32%), crowding (30%), 99% of the sample showed at least one occlusal trait. Class I molar relationship prevailed (75.5%) and the prevalence of molar asymmetries was 21.9%. The prevalence of anterior and posterior crossbite and open bite was significantly higher in females, while the mean values of overjet and overbite were higher in males. The distribution of IOTN in the study population showed that only 49.5% had no or little need of treatment, and more than one third (35.8%) were assigned a 4 or 5 score. STATISTICS: Descriptive statistics are expressed as a percentage (± confidence interval) or mean ± standard deviation, according to the nature of the variable. CONCLUSIONS: These outcomes indicate a high prevalence of the aforementioned occlusal traits and also a high need for orthodontic treatment among adolescents in Northeast Italy.


Assuntos
Má Oclusão/epidemiologia , Determinação de Necessidades de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Estudos de Coortes , Estudos Transversais , Modelos Dentários , Diastema/epidemiologia , Feminino , Humanos , Índice de Necessidade de Tratamento Ortodôntico , Itália/epidemiologia , Registro da Relação Maxilomandibular/instrumentação , Masculino , Má Oclusão de Angle Classe I/epidemiologia , Mordida Aberta/epidemiologia , Sobremordida/epidemiologia , Prevalência , Fatores Sexuais
15.
Eur J Paediatr Dent ; 17(4): 307-309, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28045319

RESUMO

AIM: To clinically evaluate the prevalence of cross-bite in a sample of 1960 children in our Local Health Unit n. 15 Alta Padovana (Veneto region, Northeast Italy). METHODS: Study design: A cross-sectional study was carried out in the area of Health District n. 15, Veneto region, including 7,364 children from 3 to 5 years, attending a total of 88 nursery schools A convenience sample of 27 nursery schools (30% of total) was randomly selected, for a total of 2,603 eligible children; of these, 1960 children formed our study base (76%). The day of examination 566 children were absent and 77 did not meet the inclusion criteria by age (less than 3 or more than 5 years old). Anterior cross-bite was considered when one or more primary or permanent mandibular incisors occluded labially to their antagonists. Posterior cross-bite (uni- or bilateral) was considered when the buccal cusps of one or more maxillary teeth was lingual to the buccal cusps of the mandibular teeth of the primary dentition. In this definition, edge to edge occlusion is not regarded as cross-bite. The examination was carried out by two calibrated dentists with children sitting on a dental chair with good operative lighting. The data were recorded in a special clinical chart. RESULTS: The prevalence of cross-bite was 3.7%. We observed a slight prevalence of cross-bite in females, but with no overall statistical significance. CONCLUSION: The prevalence of cross-bite in this area was low compared with European and American data.


Assuntos
Má Oclusão/epidemiologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Prevalência
17.
Scand J Rheumatol ; 44(4): 284-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25974389

RESUMO

OBJECTIVES: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features. METHOD: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped. RESULTS: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.001). The R63 variant was associated with increased rates of relapse (p = 0.0001). CONCLUSIONS: This study indicates that the CB2 receptor contributes to susceptibility to oligo/polyarticular JIA and to the severity of its clinical course.


Assuntos
Artrite Juvenil/genética , Artrite/genética , Variação Genética/genética , Receptor CB2 de Canabinoide/genética , Artrite/etnologia , Artrite Juvenil/etnologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Itália , Masculino , Índice de Gravidade de Doença
18.
Bone Marrow Transplant ; 50(7): 886-91, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25665044

RESUMO

Although stem cell mobilization has been performed for more than 20 years, little is known about the effects of mobilizing agents on apheresis composition and the impact of graft cell subsets on patients' outcome. With the increasing use of plerixafor and the inclusion of poor mobilizers in autologous transplant procedures, new parameters other than CD34(+) stem cell dose are emerging; plerixafor seems to mobilize more primitive CD34(+)/CD38(-) stem cells compared with G-CSF, but their correlation with stable hematopoietic engraftment is still obscure. Immune recovery is as crucial as hematopoietic reconstitution, and higher T and natural killer cells infused within the graft have been correlated with better outcome in autologous transplant; recent studies showed increased mobilization of immune effectors with plerixafor compared with G-CSF, but further data are needed to clarify the clinical impact of these findings. In the allogeneic setting, much evidence suggests that mobilized T-cell alloreactivity is tempered by G-CSF, probably with the mediation of dendritic cells, even though no clear correlation with GVL and GVHD has been found. Plerixafor is not approved in healthy donors yet; early data suggest it might mobilize a GVHD protective balance of immune effectors, but further studies are needed to define its role in allogeneic transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/imunologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Feminino , Humanos , Masculino , Resultado do Tratamento
19.
Eur J Clin Nutr ; 69(2): 211-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25293434

RESUMO

BACKGROUND/OBJECTIVES: Salt iodization is one of the preferred strategies to eradicate iodine-deficiency disorders worldwide. The aim of this study was (i) to estimate the daily iodine intake in the Italian population, (ii) to verify whether the recently recommended salt intake of 5 g/day in adults and less in children may be sufficient to achieve the adequate daily iodine intake, (iii) to estimate the contribution of iodine-enriched vegetables to the total daily iodine intake. SUBJECTS/METHODS: The content of iodine has been evaluated in 288 food samples highly representative of Italian eating habits. The contribution of foods and iodized salt to the total daily iodine intake was estimated in adults, adolescents, and children on the basis of available nationwide data of food consumption. RESULTS: The total daily iodine intake owing to food and uniodized salt consumption resulted lower than the daily requirement in all age groups. With a daily consumption of 5 g of salt iodized at 30 mg/kg, the estimated daily iodine intake resulted within the range of optimal iodine intake in all age groups. In children the recommended iodine intake is achieved with a daily consumption of 3 g of iodized salt. Moreover, the daily iodine intake significantly increased in all age groups if the consumption of iodine-enriched vegetables was considered in substitution of non iodine-enriched ones. CONCLUSIONS: Our study suggests that the recommended quantities of salt, if iodized at 30 mg/kg, are sufficient to achieve the adequate daily iodine intake both in adults and children.


Assuntos
Deficiências Nutricionais/prevenção & controle , Dieta , Iodo/administração & dosagem , Necessidades Nutricionais , Recomendações Nutricionais , Cloreto de Sódio na Dieta/administração & dosagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Alimentos Fortificados , Humanos , Lactente , Iodo/deficiência , Iodo/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Cloreto de Sódio na Dieta/uso terapêutico , Verduras , Adulto Jovem
20.
J Endocrinol Invest ; 38(2): 185-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25403430

RESUMO

PURPOSE: Although a nation-wide salt iodization program on voluntary basis was implemented in 2005, many areas in our country are still characterized by mild iodine deficiency. Differently from the rest of Italy, an efficient program of iodine prophylaxis was implemented in 1981 in the Autonomous Province of Bolzano. The aim of this study was to investigate whether an adequate iodine intake in the population may affect the incidence of permanent congenital hypothyroidism (CH). METHODS: The incidence trends of permanent CH between 1987 and 2006 in Bolzano Province and in the rest of Italy were estimated. RESULTS: Over the years, the CH incidence has remained steadily lower in Bolzano than in the rest of the country. CONCLUSIONS: Primary prevention of permanent CH may be possible by assuring an adequate nutritional iodine intake in the population. However, the time needed to observe a decrease in the incidence of CH is about a decade under conditions of iodine sufficiency.


Assuntos
Hipotireoidismo Congênito/dietoterapia , Hipotireoidismo Congênito/epidemiologia , Iodo/administração & dosagem , Cloreto de Sódio na Dieta/administração & dosagem , Pré-Escolar , Hipotireoidismo Congênito/diagnóstico , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Resultado do Tratamento
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