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1.
Ecotoxicol Environ Saf ; 272: 116015, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38290314

RESUMO

Graphene oxide (GOx) is a nanomaterial with demonstrated capacity to remove metals from water. However, its effects on organic pollutants and metal(loid)s present in polluted soils when used for remediation purposes have not been extensively addressed. Likewise, few studies describe the effects of GOx on edaphic properties and soil biology. In this context, here we assessed the potential of GOx for remediating polluted soil focusing also on different unexplored effects of GOx in soil. To achieve this, we treated soil contaminated with concurrent inorganic (As and metals) and organic pollution (TPH and PAHs), using GOx alone and in combination with nutrients (N and P sources). In both cases increased availability of As and Zn was observed after 90 days, whereas Cu and Hg availability was reduced and the availability of Pb and the concentration of organic pollutants were not significantly affected. The application of GOx on the soil induced a significant and rapid change (within 1 week) in microbial populations, leading to a transient reduction in biodiversity, consistent with the alteration of several soil properties. Concurrently, the combination with nutrients exhibited a distinct behaviour, manifesting a more pronounced and persistent shift in microbial populations without a decrease in biodiversity. On the basis of these findings, GOx emerges as a versatile amendment for soil remediation approaches.


Assuntos
Poluentes Ambientais , Grafite , Metais Pesados , Microbiota , Poluentes do Solo , Solo/química , Poluentes do Solo/análise , Metais , Metais Pesados/análise
2.
J Environ Manage ; 354: 120293, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38387345

RESUMO

The recurrence and severity of wildfire is on the rise due to factors like global warming and human activities. Mediterranean regions are prone to significant wildfire events, which cause extensive damage to ecosystems and soil properties. This study focuses on the municipality of Allande in south-western Asturias (Spain), a region highly affected by recurrent wildfires. In this regard, we sought to examine how the recurrence of such fires influences soil organic carbon fractionation and other soil parameters, such as nitrogen fractionation, pH, and cation exchange capacity. The study involved six sampling plots with between varying fire recurrence levels, from 0 to 4 events between 2005 and 2022. The results revealed some significant effects of wildfires recurrence on soil texture, inorganic elemental composition and CEC, but not on pH and CE. In soil affected by recurrent fires, labile carbon fractions (cold-water extractable & hot-water extractable), and fulvic acid concentrations decreased by up to 36%, 5%, and 45%, respectively in comparison with undisturbed soil. In contrast, humic acid concentration remained stable or increased in soils damaged by fire. Additionally, nitrogen species in soil were observed to decrease significantly in high recurrence scenarios, especially nitrate. On the basis of our findings, we conclude that wildfires impact the distinct fractions of organic carbon and nitrogen in soils and that this effect is aggravated by increasing recurrence.


Assuntos
Incêndios , Incêndios Florestais , Humanos , Solo/química , Ecossistema , Florestas , Carbono/química , Água , Nitrogênio/análise
3.
Lett Appl Microbiol ; 75(5): 1084-1092, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34608662

RESUMO

The treatment of metal-laden industrial effluents by reverse osmosis is gaining in popularity worldwide due to its high performance. However, this process generates a polymetallic concentrate (retentate) stream in need of efficient post-treatment prior to environmental discharge. This paper presents results on the bioremediation (in batch mode) of a metal-laden, arsenic-dominated retentate using Shewanella sp. O23S as inoculum. The incubation of the retentate for 14 days under anoxic conditions resulted in the following removal yields: As (8%), Co (11%), Mo (3%), Se (62%), Sb (30%) and Zn (40%). The addition of 1 mmol l-1 cysteine increased the removal rate as follows: As (27%), Co (80%), Mo (78%), Se (88%), Sb (83%) and Zn (90%). The contribution of cysteine as a source of H2 S to enhancing the removal yield was confirmed by its addition after 7 days of incubations initially lacking it. Additionally, the cysteine-sourced H2 S was confirmed by its capture onto headspace-mounted Pb-acetate test strips that were analysed by X-ray diffraction. We show that real metal-laden industrial effluents can be treated to medium-to-high efficiency using a biological system (naturally sourced inocula) and inexpensive reagents (yeast extract, lactate and cysteine).


Assuntos
Arsênio , Purificação da Água , Arsênio/análise , Biodegradação Ambiental , Purificação da Água/métodos , Rios , Cisteína , Chumbo , Osmose , Lactatos
4.
Exp Appl Acarol ; 87(4): 325-335, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35984583

RESUMO

Predatory mite species (Acari: Phytoseiidae) are essential tools in the biological control of greenhouses pests. The natural enemies can be released directly into a crop. A better, partly preventive system is to place slow-release sachets on the plants. Inside such sachets is a factitious prey's food substrate-which also acts as refuge-and the predator. The objective of this study was to develop a new methodology to evaluate the population dynamics of this sachet system, based on the factitious prey Carpoglyphus lactis and the predatory mite Amblyseius swirskii. Through two tests carried out under laboratory conditions, the sachets were first compared to the traditional extraction method that uses Berlese-Tullgren funnels and an extraction method using flotation in hexane. The latter method proved more effective at sampling the motile states (larvae, nymphs, and adults), both for the predatory species and for the factitious prey, extracting up to 3.7 × more mites than the Berlese-Tullgren funnel. Second, the population dynamics of both mite species was studied in a laboratory test, both inside and outside the sachets. In this way, a positive correlation was demonstrated between the number of predatory mites and the number of prey mites inside the sachets. Conversely, no correlation was found between the interior population of predatory mites and the number that venture outside. We can conclude that hexane extraction is very useful both in quality control of predatory mites and in studying how the sachets behave when faced with various factors.


Assuntos
Ácaros , Animais , Hexanos , Ninfa , Controle Biológico de Vetores/métodos , Dinâmica Populacional , Comportamento Predatório
5.
Allergol Immunopathol (Madr) ; 49(6): 48-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761656

RESUMO

INTRODUCTION: There is an increasing amount of data relating the dietetic pattern to health variables, although data concerning the child population are scarce. The aim of the study was to assess the effects of affinity to the Traditional Mediterranean Diet (TMD) pattern, together with breastfeeding, on the incidence of childhood asthma and other inflammatory and recurrent diseases (IRD) in children under 2 years of age. METHODS: Single-group intervention study evaluating differences in results according to degree of adherence to TMD recommendations. According to their adhesion to the TMD-Breastfed Test, patients were classified into two groups: Group 1 (with greater adherence) and Group 2 (with less adherence). The incidence of childhood asthma and IRD was evaluated and compared with both groups. RESULTS: The score of the TMD-Breastfed Test was optimal in Group 1 and good in Group 2. It shows a marked reduction in both consultation groups "on request" compared with "planned," with low morbidity and low use of antibiotics. The incidence of infectious diseases and recurrent bacterial complications shows a clinically relevant difference between both groups. The incidence of childhood asthma was greater and statistically significant in Group 2, with less adherence to breastfeeding. CONCLUSIONS: In these cohorts of breastfed patients with good adherence to TMD patterns, there was evidence of a low incidence of childhood asthma and the IRD, more pronounced in the highest adherence Group 1. Some non-TMD foods have been linked to the occurrence of childhood asthma and IRD, as their dietary limitations have contributed to decreasing morbidity.


Assuntos
Asma , Aleitamento Materno , Dieta Mediterrânea , Asma/epidemiologia , Criança , Feminino , Humanos , Incidência , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente
6.
Ann Oncol ; 30(3): 439-446, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30689692

RESUMO

BACKGROUND: Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from antiepidermal growth factor receptor (EGFR) therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive next-generation sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-vascular endothelial growth factor. PATIENTS AND METHODS: Five hundred and eighty-one tumour samples from untreated mCRC patients from 7 clinical studies were collected. Mutational analysis was carried out by standard-of-care (therascreen pyro) with a sensitivity detection of 5% mutant allele fraction (MAF), and compared with NGS technology using 454GS Junior platform (Roche Applied Science, Germany) with a sensitivity of 1%. Molecular results were correlated with clinical outcomes. RESULTS: After quality assessment, 380 samples were evaluable for molecular analysis. Standard-of-care mutational analysis detected RAS, BRAFV600E or PIK3CA mutations in 56.05% of samples compared with 69.21% by NGS (P = 0.00018). NGS identified coexistence of multiple low-frequency mutant alleles in 96 of the 263 mutated cases (36.5%; range 2-7). Response rate (RR), progression-free survival (PFS) and overall survival (OS) were increasingly improved in patients with RAS wild-type, RAS/BRAF wild-type or quadruple (KRAS/NRAS/BRAF/PIK3CA) wild-type tumours treated with anti-EGFR, assessed by standard-of-care. No additional benefit in RR, PFS or OS was observed by increasing the detection threshold to 1% by NGS. An inverse correlation between the MAF of the most prevalent mutation detected by NGS and anti-EGFR response was observed (P = 0.039). EGFRS492Rmutation was not detected in untreated samples. CONCLUSIONS: No improvement in the selection of patients for anti-EGFR therapy was obtained by adjusting the mutation detection threshold in tissue samples from 5% to 1% MAF. Response to anti-EGFR was significantly better in patients with quadruple wild-type tumours.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cetuximab/administração & dosagem , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Alemanha , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Metástase Neoplásica , Inibidores de Proteínas Quinases/administração & dosagem , Resultado do Tratamento
7.
Phys Rev Lett ; 122(17): 176801, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31107081

RESUMO

The discretization of the electronic structure of nanometer-size solid systems due to quantum confinement and the concomitant modification of their physical properties is one of the cornerstones for the development of nanoscience and nanotechnology. In this Letter we demonstrate that the Bragg scattering of Cu(111) surface-state electrons by the periodic arrangement of tetracyanoquinodimethane molecules at the edges of self-assembled molecular islands, along with the dominant contribution of backscattering processes to the electronic density of states, discretizes the possible values of the electron momentum parallel to the island edge. The electronic structure consists thus of a discrete number of subbands which occur in a nonclosed space, and therefore without quantum confinement.

8.
BMC Cancer ; 19(1): 533, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159765

RESUMO

BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Idoso Fragilizado , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Astenia/etiologia , Neoplasias Colorretais/mortalidade , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Hipofosfatemia/etiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos de Fenilureia/administração & dosagem , Projetos Piloto , Intervalo Livre de Progressão , Piridinas/administração & dosagem , Espanha , Resultado do Tratamento
9.
Mol Psychiatry ; 23(3): 701-707, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28348381

RESUMO

Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Adulto , Antipsicóticos/uso terapêutico , Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Espaço Extracelular/diagnóstico por imagem , Feminino , Previsões/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Transtornos Neurocognitivos/diagnóstico por imagem , Esquizofrenia/patologia , Resultado do Tratamento , Água/análise , Substância Branca/patologia , Adulto Jovem
10.
Int J Mol Sci ; 20(3)2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30696068

RESUMO

Despite recent therapeutic advances, systemic mastocytosis (SM) remains an incurable disease due to limited complete remission (CR) rates even after novel therapies. To date, no study has evaluated the expression on SM bone marrow mast cells (BMMC) of large panel of cell surface suitable for antibody-targeted therapy. In this study, we analyzed the expression profile of six cell-surface proteins for which antibody-based therapies are available, on BMMC from 166 SM patients vs. 40 controls. Overall, variable patterns of expression for the markers evaluated were observed among SM BMMC. Thus, CD22, CD30, and CD123, while expressed on BMMC from patients within every subtype of SM, showed highly variable patterns with a significant fraction of negative cases among advanced SM (aggressive SM (ASM), ASM with an associated clonal non-MC lineage disease (ASM-AHN) and MC leukemia (MCL)), 36%, 46%, and 39%, respectively. In turn, CD25 and FcεRI were found to be expressed in most cases (89% and 92%) in virtually all BMMC (median: 92% and 95%) from both indolent and advanced SM, but with lower/absent levels in a significant fraction of MC leukemia (MCL) and both in MCL and well-differentiated SM (WDSM) patients, respectively. In contrast, CD33 was the only marker expressed on all BMMC from every SM patient. Thus, CD33 emerges as the best potentially targetable cell-surface membrane marker in SM, particularly in advanced SM.


Assuntos
Anticorpos/metabolismo , Células da Medula Óssea/metabolismo , Membrana Celular/metabolismo , Mastócitos/metabolismo , Mastocitose Sistêmica/metabolismo , Humanos , Imunofenotipagem , Mastocitose Sistêmica/diagnóstico , Prognóstico
11.
Ann Oncol ; 29(2): 439-444, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29145602

RESUMO

Background: There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC. Patients and methods: This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point. Results: Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group. Conclusions: This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC. ClinicalTrials.gov: NCT01071655.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Testes Farmacogenômicos/métodos , Variantes Farmacogenômicos/genética , Timidilato Sintase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Resultado do Tratamento
12.
Phys Rev Lett ; 121(17): 173603, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30411925

RESUMO

We observe a sixfold Purcell broadening of the D_{2} line of an optically trapped ^{87}Rb atom strongly coupled to a fiber cavity. Under external illumination by a near-resonant laser, up to 90% of the atom's fluorescence is emitted into the resonant cavity mode. The sub-Poissonian statistics of the cavity output and the Purcell enhancement of the atomic decay rate are confirmed by the observation of a strongly narrowed antibunching dip in the photon autocorrelation function. The photon leakage through the higher-transmission mirror of the single-sided resonator is the dominant contribution to the field decay (κ≈2π×50 MHz), thus offering a high-bandwidth, fiber-coupled channel for photonic interfaces such as quantum memories and single-photon sources.

13.
Allergy ; 73(6): 1294-1304, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29331029

RESUMO

BACKGROUND: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation. METHODS: The distribution of different maturation-associated subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS-purified PB cell compartments were also investigated for the KIT mutation. RESULTS: ISM patients showed higher percentages of both BM and PB MC-committed CD34+ HPC vs controls, particularly among ISM cases with MC-restricted KIT mutation (ISMMC ); this was associated with progressive blockade of maturation of CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases (ISMML ). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34+ HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs-MC and ISMs+MC to ISMML patients. CONCLUSION: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34+ HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34+ HPC potentially contributing to early dissemination of the disease.


Assuntos
Células-Tronco Hematopoéticas/metabolismo , Mastocitose Sistêmica/etiologia , Mastocitose Sistêmica/metabolismo , Alelos , Antígenos CD34/metabolismo , Biomarcadores , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Diferenciação Celular/genética , Feminino , Genótipo , Células-Tronco Hematopoéticas/citologia , Humanos , Imunofenotipagem , Leucócitos/citologia , Leucócitos/metabolismo , Masculino , Mastocitose Sistêmica/diagnóstico , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Espanha
14.
Gastric Cancer ; 21(1): 96-105, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28393278

RESUMO

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sistema de Registros
15.
Br J Cancer ; 116(12): 1526-1535, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463962

RESUMO

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Nível de Saúde , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Gradação de Tumores , Neutrófilos , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Trastuzumab/administração & dosagem , Carga Tumoral , População Branca , Adulto Jovem
16.
Br J Cancer ; 117(6): 775-782, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28765618

RESUMO

BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). METHODS: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. RESULTS: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Antraciclinas/administração & dosagem , Chile , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Receptor ErbB-2 , Espanha , Neoplasias Gástricas/classificação , Taxoides/administração & dosagem , Resultado do Tratamento
17.
Phys Rev Lett ; 119(18): 180503, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29219582

RESUMO

We demonstrate the parallel and nondestructive readout of the hyperfine state for optically trapped ^{87}Rb atoms. The scheme is based on state-selective fluorescence imaging and achieves detection fidelities >98% within 10 ms, while keeping 99% of the atoms trapped. For the readout of dense arrays of neutral atoms in optical lattices, where the fluorescence images of neighboring atoms overlap, we apply a novel image analysis technique using Bayesian inference to determine the internal state of multiple atoms. Our method is scalable to large neutral atom registers relevant for future quantum information processing tasks requiring fast and nondestructive readout and can also be used for the simultaneous readout of quantum information stored in internal qubit states and in the atoms' positions.

18.
Psychol Med ; 47(10): 1706-1718, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28193301

RESUMO

BACKGROUND: Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. METHOD: A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1-3, posterior CA1-3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability. RESULTS: Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans. CONCLUSIONS: This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.


Assuntos
Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Hipocampo , Transtornos Psicóticos/tratamento farmacológico , Risperidona/farmacologia , Adulto , Antipsicóticos/administração & dosagem , Aripiprazol/administração & dosagem , Giro Denteado/diagnóstico por imagem , Giro Denteado/efeitos dos fármacos , Giro Denteado/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Risperidona/administração & dosagem , Adulto Jovem
19.
Acta Neurol Scand ; 136(5): 393-400, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28261780

RESUMO

OBJECTIVES: Patients with Parkinson's disease (PD) and essential tremor (ET) have a higher risk of cognitive impairment than age-matched controls. Only a few small studies (11-18 subjects per group) have directly compared the cognitive profile of these conditions. Our aim was to compare the cognitive profile of patients with these two conditions to each other and to healthy individuals in a population-based study of non-demented participants. MATERIALS AND METHODS: This investigation was part of the NEDICES study, a survey of the elderly in which 2438 dementia-free participants underwent a short neuropsychological battery. We used nonparametric techniques to evaluate whether there are differences and/or a gradient of impairment across the groups (PD, ET, and controls). Also, we performed a head-to-head comparison of ET and PD, adjusting for age and education. RESULTS: Patients with PD (N=46) and ET (N=180) had poorer cognition than controls (N=2212). An impaired gradient of performance was evident. PD scored lower than ET, and then each of these lower than controls, in memory (P<.05) and verbal fluency (P<.001) tasks. When we compared PD and ET, the former had lower scores in verbal fluency (P<.05), whereas the later had a poorer cognitive processing speed (P<.05). CONCLUSIONS: This large population-based study demonstrates that both conditions influence cognitive performance, that a continuum exists from normal controls to ET to PD (most severe), and that although deficits are in many of the same cognitive domains, the affected cognitive domains do not overlap completely.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/psicologia , Tremor Essencial/psicologia , Doença de Parkinson/psicologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/complicações , Tremor Essencial/complicações , Feminino , Humanos , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações
20.
Phys Chem Chem Phys ; 19(12): 8282-8287, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28277577

RESUMO

Single-molecule magnets based on lanthanide double-deckers are attracting significant attention due to their unrivaled single-ion anisotropy. To exploit their fascinating electronic and magnetic properties in devices for information storage or spin transport, studies on the preservation or variation of electronic and magnetic functionalities upon adsorption on surfaces are necessary. Herein, we introduced a comprehensive scanning tunneling microscopy (STM) and X-ray photoelectron spectroscopy (XPS) surface science study, complemented by density functional theory (DFT) simulations, of a recently synthesized single-molecule magnet based on porphyrazine deckers, conveniently equipped with ethyl moieties to make them soluble and sublimable. We demonstrated that the double-decker species were intactly adsorbed on Au(111), Ag(111), and Cu(111) in a flat-on fashion and self-assembled in hexagonal close-packed layers. Systematic multi- and monolayer XPS was performed on the surface-confined species, confirming the preservation of the electronic properties of the ligands and the lanthanide center upon adsorption.

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