Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
1.
Gut ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980446

RESUMO

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM). OBJECTIVE: To identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM. DESIGN: We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4- cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. RESULTS: MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. CONCLUSION: Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.

2.
Proc Natl Acad Sci U S A ; 117(6): 2930-2937, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31980533

RESUMO

Scaffold proteins organize cellular processes by bringing signaling molecules into interaction, sometimes by forming large signalosomes. Several of these scaffolds are known to polymerize. Their assemblies should therefore not be understood as stoichiometric aggregates, but as combinatorial ensembles. We analyze the combinatorial interaction of ligands loaded on polymeric scaffolds, in both a continuum and discrete setting, and compare it with multivalent scaffolds with fixed number of binding sites. The quantity of interest is the abundance of ligand interaction possibilities-the catalytic potential Q-in a configurational mixture. Upon increasing scaffold abundance, scaffolding systems are known to first increase opportunities for ligand interaction and then to shut them down as ligands become isolated on distinct scaffolds. The polymerizing system stands out in that the dependency of Q on protomer concentration switches from being dominated by a first order to a second order term within a range determined by the polymerization affinity. This behavior boosts Q beyond that of any multivalent scaffold system. In addition, the subsequent drop-off is considerably mitigated in that Q decreases with half the power in protomer concentration than for any multivalent scaffold. We explain this behavior in terms of how the concentration profile of the polymer-length distribution adjusts to changes in protomer concentration and affinity. The discrete case turns out to be similar, but the behavior can be exaggerated at small protomer numbers because of a maximal polymer size, analogous to finite-size effects in bond percolation on a lattice.

3.
Haematologica ; 105(3): 838-848, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31171643

RESUMO

Randomized clinical trials have evaluated the role of anticoagulants in the prevention of venous thromboembolism (VTE) in ambulatory cancer patients treated with chemotherapy. This meta-analysis is aimed at providing an updated evaluation of the efficacy and safety of anticoagulant prophylaxis in this clinical setting. Medline and Scopus were searched to retrieve randomized controlled trials on the prevention of VTE in ambulatory cancer patients. Two groups of trials were identified with VTE or death as the primary outcome, respectively. VTE was the primary outcome of this analysis. Anticoagulant prophylaxis reduced the incidence of VTE in studies in which the primary outcome was VTE [14 studies, 8,226 patients; odds ratio (OR)=0.45; 95% confidence interval (95% CI): 0.36-0.56] or death (8 studies, 3,727 patients; OR=0.61; 95% CI: 0.47-0.81). When these studies were pooled together, VTE was reduced by 49% (95% CI: 0.43-0.61) with no significant increase in major bleeding (OR=1.30, 95% CI: 0.98-1.73). The risk of major bleeding was increased in studies with VTE as the primary outcome (OR=1.43, 95% CI: 1.01-2.04). Similar reductions of VTE were observed in studies with parenteral (OR=0.43, 95% CI: 0.33-0.56) or oral anticoagulants (OR=0.49, 95% CI: 0.33-0.74). The reduction in VTE was confirmed in patients with lung (OR=0.42, 95% CI: 0.26-0.67) or pancreatic cancer (OR=0.26, 95% CI: 0.14-0.48), in estimated high-risk patients, in high-quality studies and with respect to symptomatic VTE. In conclusion, prophylaxis with oral or parenteral anticoagulants reduces the risk of VTE in ambulatory cancer patients, with an acceptable increase in major bleeding.

4.
J Sci Food Agric ; 100(2): 714-720, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31597200

RESUMO

BACKGROUND: Longitudinal data analysis contributes to detect differences in the growing curve by exploiting all the information involved in repeated measurements, allowing to distinguish changes over time within individuals, from differences in the baseline levels among groups. In this research, longitudinal and cross-sectional analysis were compared to evaluate differences in growth in Angus heifers under two different grazing conditions, ad libitum (AG) and controlled (CG) to gain 0.5 kg day-1 . RESULTS: Longitudinal mixed models show differences in growing curve parameters between grazing conditions, that were not detected by cross-sectional analysis. Differences (P < 0.05) in first derivative of growth curves (daily gain) until 289 days were observed between treatments, AG being higher than CG. Correspondingly, pubertal heifer proportion was also higher in AG at the end of rearing (AG, 0.94; CG, 0.67). CONCLUSION: In longitudinal studies, the power to detect differences between groups increases by exploiting the whole information of repeated measures, modelling the relation between measurements performed on the same individual. Under a proper analysis, valid conclusion can be drawn with fewer animals in the trial, improving animal welfare and reducing investigation costs. © 2019 Society of Chemical Industry.


Assuntos
Ração Animal/análise , Bovinos/crescimento & desenvolvimento , Bovinos/metabolismo , Criação de Animais Domésticos , Animais , Cruzamento , Bovinos/genética , Estudos Transversais , Análise de Dados , Comportamento Alimentar , Feminino , Estudos Longitudinais , Masculino , Poaceae/metabolismo
5.
Sensors (Basel) ; 19(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717423

RESUMO

Road traffic pollution is one of the key factors affecting urban air quality. There is a consensus in the community that the efficient use of public transport is the most effective solution. In that sense, much effort has been made in the data mining discipline to come up with solutions able to anticipate taxi demands in a city. This helps to optimize the trips made by such an important urban means of transport. However, most of the existing solutions in the literature define the taxi demand prediction as a regression problem based on historical taxi records. This causes serious limitations with respect to the required data to operate and the interpretability of the prediction outcome. In this paper, we introduce QUADRIVEN (QUalitative tAxi Demand pRediction based on tIme-Variant onlinE social Network data analysis), a novel approach to deal with the taxi demand prediction problem based on human-generated data widely available on online social networks. The result of the prediction is defined on the basis of categorical labels that allow obtaining a semantically-enriched output. Finally, this proposal was tested with different models in a large urban area, showing quite promising results with an F1 score above 0.8.

6.
Lancet Oncol ; 20(10): e566-e581, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31492632

RESUMO

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

7.
Sci Rep ; 9(1): 11486, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391486

RESUMO

Cattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development.

8.
Sensors (Basel) ; 19(14)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336686

RESUMO

The constant innovation in new technologies and the increase in the use of computing devices in different areas of the society have contributed to a digital transformation in almost every sector. This digital transformation has also reached the world of education, making it possible for members of the educational community to adopt Learning Management Systems (LMS), where the digital contents replacing the traditional textbooks are exploited and managed. This article aims to study the relationship between the type of computing device from which students access the LMS and how affects their performance. To achieve this, the LMS accesses of students in a school comprising from elementary to bachelor's degree stages have been monitored by means of different computing devices acting as sensors to gather data such as the type of device and operating system used by the students.The main conclusion is that students who access the LMS improve significantly their performance and that the type of device and the operating system has an influence in the number of passed subjects. Moreover, a predictive model has been generated to predict the number of passed subjects according to these factors, showing promising results.


Assuntos
Instrução por Computador/instrumentação , Adolescente , Criança , Instrução por Computador/métodos , Instrução por Computador/estatística & dados numéricos , Computadores , Feminino , Humanos , Masculino , Instituições Acadêmicas , Smartphone , Estudantes
9.
Thromb Res ; 181: 59-63, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352267

RESUMO

BACKGROUND: The Ottawa score was previously developed to predict recurrent venous thromboembolism (VTE) in cancer patients with VTE. The performance of this score in patients with incidental VTE is currently unclear. AIM: To evaluate the performance of the Ottawa risk score in cancer patients with incidental pulmonary embolism included in an international, prospective, observational cohort study. METHODS: The score was used to classify patients as high (≥1), intermediate (0), or low risk (≤-1). The discriminative performance of the score was estimated by calculating the cumulative incidence of recurrent VTE for all groups, the time-dependent c-statistic, and the sub-distribution hazard ratio (SHR), using a competing risk approach. RESULTS: Of the 691 patients for which the Ottawa score could be calculated, 25 (3.6%) had recurrent VTE during 6-month follow-up and 38 (5.5%) during 12-month follow-up. The c-statistics of the continuous score at 6 and 12 months were 0.45 (95% CI, 0.36-0.54) and 0.51 (95% CI, 0.46-0.59), respectively. The 6-month cumulative incidences of recurrent VTE for those at low, intermediate, and high risk were 3.9% (95% CI, 1.5-8.4), 3.6% (95% CI, 1.9-6.2), and 3.6% (95% CI, 1.8-6.5), respectively. A sensitivity analysis restricted to the on-treatment period yielded similar results. None of the Ottawa risk score items were significantly associated with recurrent VTE. CONCLUSION: In cancer patients with incidental pulmonary embolism, the Ottawa risk score has a poor predictive value for recurrent VTE, which does not support the use of the score in this patient population.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/complicações , Embolia Pulmonar/etiologia , Tromboembolia Venosa/etiologia , Idoso , Anticoagulantes/farmacologia , Feminino , Humanos , Masculino , Embolia Pulmonar/patologia , Tromboembolia Venosa/patologia
10.
J Clin Oncol ; 37(20): 1713-1720, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31116676

RESUMO

PURPOSE: Pulmonary embolism is incidentally diagnosed in up to 5% of patients with cancer on routine imaging scans. The clinical relevance and optimal therapy for incidental pulmonary embolism, particularly distal clots, is unclear. The aim of the current study was to assess current treatment strategies and the long-term clinical outcomes of incidentally detected pulmonary embolism in patients with cancer. PATIENTS AND METHODS: We conducted an international, prospective, observational cohort study between October 22, 2012, and December 31, 2017. Unselected adults with active cancer and a recent diagnosis of incidental pulmonary embolism were eligible. Outcomes were recurrent venous thromboembolism, major bleeding, and all-cause mortality during 12 months of follow-up. Outcome events were centrally adjudicated. RESULTS: A total of 695 patients were included. Mean age was 66 years and 58% of patients were male. Most frequent cancer types were colorectal (21%) and lung cancer (15%). Anticoagulant therapy was initiated in 675 patients (97%), of whom 600 (89%) were treated with low-molecular-weight heparin. Recurrent venous thromboembolism occurred in 41 patients (12-month cumulative incidence, 6.0%; 95% CI, 4.4% to 8.1%), major bleeding in 39 patients (12-month cumulative incidence, 5.7%; 95% CI, 4.1% to 7.7%), and 283 patients died (12-month cumulative incidence, 43%; 95% CI, 39% to 46%). The 12-month incidence of recurrent venous thromboembolism was 6.4% in those with subsegmental pulmonary embolism compared with 6.0% in those with more proximal pulmonary embolism (subdistribution hazard ratio, 1.1; 95% CI, 0.37 to 2.9; P = .93). CONCLUSION: In patients with cancer with incidental pulmonary embolism, risk of recurrent venous thromboembolism is significant despite anticoagulant treatment. Patients with subsegmental pulmonary embolism seemed to have a risk of recurrent venous thromboembolism comparable to that of patients with more proximal clots.

11.
Exp Eye Res ; 184: 24-29, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30980815

RESUMO

The purpose of the study is to evaluate the protective properties of PEDF peptide fragments on rd10 mouse models of retinal degeneration ex vivo. Human recombinant PEDF and synthetic peptides were used. Rd10 retinal explants as well as wild-type retinal explants treated with zaprinast to mimic the rd10 photoreceptor cell death were employed. PEDF protein was intravitreally administered into rd10 mice. Outer nuclear layer thickness measurements in retinal sections, TUNEL labeling in retinal explants, western blots and immunofluorescence with retinal samples were performed. PEDF protein levels in the RPE of rd10 mice decreased with age (P15 - P25). Levels of PEDF receptor PEDF-R declined in the photoreceptor inner segments from rd10 relative to wild-type mice at P25. PEDF administration increased the outer nuclear layer thickness of rd10 retinas in vivo and decreased the number of TUNEL+ nuclei of photoreceptors in rd10 retinal explant cultures, both relative to untreated controls. Peptides containing the PEDF neurotrophic region decreased the number of TUNEL+ photoreceptors in both rd10 and zaprinast-induced cell death ex vivo models, while peptides without the neurotrophic region and/or lacking affinity for PEDF-R were ineffective in protecting photoreceptors. Thus, retinal explants are a valuable system to evaluate PEDF activity. Short peptides with the photoreceptor-protective property of PEDF may prove useful for the development of therapeutic agents for photoreceptor protection in retinal degenerations.


Assuntos
Proteínas do Olho/uso terapêutico , Fatores de Crescimento Neural/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Degeneração Retiniana/tratamento farmacológico , Serpinas/uso terapêutico , Animais , Western Blotting , Sobrevivência Celular , Modelos Animais de Doenças , Técnica Indireta de Fluorescência para Anticorpo , Marcação In Situ das Extremidades Cortadas , Injeções Intravítreas , Camundongos , Camundongos Endogâmicos C57BL , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Proteínas Recombinantes , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia
12.
Expert Opin Biol Ther ; 19(5): 411-422, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30887844

RESUMO

INTRODUCTION: The combination of oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (FOLFOXIRI) results in improved outcomes compared with standard chemotherapy when used in frontline to treat patients with metastatic colorectal cancer (mCRC). FOLFOXIRI has been recently combined with biologic agents aiming further improvement in outcomes. AREAS COVERED: This manuscript provides a comprehensive review of the results achieved by the FOLFOXIRI+biologic combination when used as first-line treatment in patients with mCRC. The search retrieved 19 clinical trial reports and 7 ongoing trials. The results are discussed focusing on secondary resection of metastatic disease, impact of sidedness (right-left primary tumor site), and impact of biomarkers. EXPERT OPINION: Panitumumab is the only biologic that has proved its value when added to FOLFOXIRI in a randomized clinical trial. FOLFOXIRI-bevacizumab has the widest data from two large randomized phase III trials, being an option to be used in both the palliative and the conversion-therapy settings. However, the true benefit from adding bevacizumab remains to be established as it has not been evaluated in a randomized setting yet. Data on response rates and secondary resection rates are promising with the FOLFOXIRI-anti-EGFR combinations and may constitute a valuable option. Results of ongoing head-to-head studies will shed additional light on this issue.

13.
BMC Evol Biol ; 19(1): 27, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654737

RESUMO

BACKGROUND: The plasminogen (PLG) activation system is composed by a series of serine proteases, inhibitors and several binding proteins, which together control the temporal and spatial generation of the active serine protease plasmin. As this proteolytic system plays a central role in human physiology and pathophysiology it has been extensively studied in mammals. The serine proteases of this system are believed to originate from an ancestral gene by gene duplications followed by domain gains and deletions. However, the identification of ancestral forms in primitive chordates supporting these theories remains elusive. In addition, evolutionary studies of the non-proteolytic members of this system are scarce. RESULTS: Our phylogenetic analyses place lamprey PLG at the root of the vertebrate PLG-group, while lamprey PLG-related growth factors represent the ancestral forms of the jawed-vertebrate orthologues. Furthermore, we find that the earliest putative orthologue of the PLG activator group is the hyaluronan binding protein 2 (HABP2) gene found in lampreys. The prime plasminogen activators (tissue- and urokinase-type plasminogen activator, tPA and uPA) first occur in cartilaginous fish and phylogenetic analyses confirm that all orthologues identified compose monophyletic groups to their mammalian counterparts. Cartilaginous fishes exhibit the most ancient vitronectin of all vertebrates, while plasminogen activator inhibitor 1 (PAI-1) appears for the first time in cartilaginous fishes and is conserved in the rest of jawed vertebrate clades. PAI-2 appears for the first time in the common ancestor of reptiles and mammals, and represents the latest appearing plasminogen activator inhibitor. Finally, we noted that the urokinase-type plasminogen activator receptor (uPAR)-and three-LU domain containing genes in general-occurred later in evolution and was first detectable after coelacanths. CONCLUSIONS: This study identifies several primitive orthologues of the mammalian plasminogen activation system. These ancestral forms provide clues to the origin and diversification of this enzyme system. Further, the discovery of several members-hitherto unknown in mammals-provide new perspectives on the evolution of this important enzyme system.


Assuntos
Cordados/genética , Variação Genética , Filogenia , Plasminogênio/genética , Sequência de Aminoácidos , Animais , Bases de Dados de Proteínas , Humanos , Funções Verossimilhança , Inibidor 1 de Ativador de Plasminogênio/química , Domínios Proteicos , Análise de Sequência de RNA , Transcriptoma/genética , Ativador de Plasminogênio Tipo Uroquinase/química , Vitronectina/química
14.
J Biol Chem ; 294(10): 3794-3805, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30651349

RESUMO

Protein sequences of members of the plasminogen activation system are present throughout the entire vertebrate phylum. This important and well-described proteolytic cascade is governed by numerous protease-substrate and protease-inhibitor interactions whose conservation is crucial to maintaining unchanged protein function throughout evolution. The pressure to preserve protein-protein interactions may lead to either co-conservation or covariation of binding interfaces. Here, we combined covariation analysis and structure-based prediction to analyze the binding interfaces of urokinase (uPA):plasminogen activator inhibitor-1 (PAI-1) and uPA:plasminogen complexes. We detected correlated variation between the S3-pocket-lining residues of uPA and the P3 residue of both PAI-1 and plasminogen. These residues are known to form numerous polar interactions in the human uPA:PAI-1 Michaelis complex. To test the effect of mutations that correlate with each other and have occurred during mammalian diversification on protein-protein interactions, we produced uPA, PAI-1, and plasminogen from human and zebrafish to represent mammalian and nonmammalian orthologs. Using single amino acid point substitutions in these proteins, we found that the binding interfaces of uPA:plasminogen and uPA:PAI-1 may have coevolved to maintain tight interactions. Moreover, we conclude that although the interaction areas between protease-substrate and protease-inhibitor are shared, the two interactions are mechanistically different. Compared with a protease cleaving its natural substrate, the interaction between a protease and its inhibitor is more complex and involves a more fine-tuned mechanism. Understanding the effects of evolution on specific protein interactions may help further pharmacological interventions of the plasminogen activation system and other proteolytic systems.


Assuntos
Evolução Molecular , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativadores de Plasminogênio/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Modelos Moleculares , Ativadores de Plasminogênio/antagonistas & inibidores , Ativadores de Plasminogênio/química , Ligação Proteica , Conformação Proteica , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
15.
Ambio ; 48(4): 350-362, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30128860

RESUMO

In January 2017, hundreds of fires in Mediterranean Chile burnt more than 5000 km2, an area nearly 14 times the 40-year mean. We contextualize these fires in terms of estimates of global fire intensity using MODIS satellite record, and provide an overview of the climatic factors and recent changes in land use that led to the active fire season and estimate the impact of fire emissions to human health. The primary fire activity in late January coincided with extreme fire weather conditions including all-time (1979-2017) daily records for the Fire Weather Index (FWI) and maximum temperature, producing some of the most energetically intense fire events on Earth in the last 15-years. Fire activity was further enabled by a warm moist growing season in 2016 that interrupted an intense drought that started in 2010. The land cover in this region had been extensively modified, with less than 20% of the original native vegetation remaining, and extensive plantations of highly flammable exotic Pinus and Eucalyptus species established since the 1970s. These plantations were disproportionally burnt (44% of the burned area) in 2017, and associated with the highest fire severities, as part of an increasing trend of fire extent in plantations over the past three decades. Smoke from the fires exposed over 9.5 million people to increased concentrations of particulate air pollution, causing an estimated 76 premature deaths and 209 additional admissions to hospital for respiratory and cardiovascular conditions. This study highlights that Mediterranean biogeographic regions with expansive Pinus and Eucalyptus plantations and associated rural depopulation are vulnerable to intense wildfires with wide ranging social, economic, and environmental impacts, which are likely to become more frequent due to longer and more extreme wildfire seasons.


Assuntos
Fogo , Pinus , Chile , Secas , Humanos , Tempo (Meteorologia)
16.
BMC Cancer ; 18(1): 1185, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30497432

RESUMO

BACKGROUND: Treatment with nab-paclitaxel plus gemcitabine increases survival in patients with metastatic pancreatic cancer. However, the assessment of treatment efficacy and safety in non-selected patients in a real-life setting may provide useful information to support decision-making processes in routine practice. METHODS: Retrospective, multicenter study including patients with metastatic pancreatic cancer, who started first-line treatment with nab-paclitaxel plus gemcitabine between December 2013 and June 2015 according to routine clinical practice. In addition to describing the treatment pattern, overall survival (OS) and progression-free survival (PFS) were assessed for the total sample and the exploratory subgroups based on the treatment and patients' clinical characteristics. RESULTS: All 210 eligible patients had a median age of 65.0 years (range 37-81). Metastatic pancreatic adenocarcinoma was recurrent in 46 (21.9%) patients and de novo in 164 (78.1%); 38 (18%) patients had a biliary stent. At baseline, 33 (18.1%) patients had an ECOG performance status ≥2. Patients received a median of four cycles of treatment (range 1-21), with a median duration of 3.5 months; 137 (65.2%) patients had a dose reduction of nab-paclitaxel and/or gemcitabine during treatment, and 33 (17.2%) discontinued treatment due to toxicity. Relative dose intensity (RDI) for nab-paclitaxel, gemcitabine, and the combined treatment was 66.7%. Median OS was 7.2 months (95% CI 6.0-8.5), and median PFS was 5.0 months (95% CI 4.3-5.9); 50 patients achieved either a partial or complete response (ORR 24.6%). OS was influenced by baseline ECOG PS, NLR and CA 19.9, but not by age ≥ 70 years and/or the presence of hepatobiliary stent or RDI < 85%. All included variables, computed as dichotomous, showed a significant contribution to the Cox regression model to build a nomogram for predicting survival in these patients: baseline ECOG 0-1 vs. 2-3 (p = 0.030), baseline NLR > 3 vs. ≤ 3 (p = 0.043), and baseline CA 19.9 > 37 U/mL vs. ≤37 U/mL (p = 0.004). CONCLUSIONS: Nab-Paclitaxel plus gemcitabine remain effective in a real-life setting, despite the high burden of dose reductions and poorer performance of these patients. A nomogram to predict survival using baseline ECOG performance status, NLR and CA 19.9 is proposed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Comorbidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
Rev. mex. trastor. aliment ; 9(2): 264-276, jul.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-978742

RESUMO

Resumen Evaluar los hábitos de salud relacionados con el sobrepeso y la obesidad infantil resulta fundamental para la prevención de estas problemáticas. Existe una amplia variedad de instrumentos para medir dichos hábitos, siendo más comunes y costo-eficientes los cuestionarios de autorreporte, sin embargo estos generan información demasiado extensa y difícil de analizar. Por tanto, este estudio tuvo como objetivo desarrollar una propuesta de síntesis de la información obtenida del Cuestionario de Hábitos de Salud relacionados con el Sobrepeso/Obesidad Infantil (CHS-SO), a partir de la construcción de indicadores de hábitos de alimentación, de actividad física y de consumo de entretenimiento digital que permitan clasificar a los niños como saludables o no saludables. Participaron 239 niños y niñas de 8 a 12 años de edad, quienes completaron el CHS-SO. La combinación del análisis de correspondencias múltiples con el de conglomerados arrojó dos clústers. Los hábitos de alimentación fueron saludables en la mayoría de los niños, sin embargo fueron identificadas diferencias en función del sexo y el nivel socioeconómico. Por el contrario, los dos hábitos menos saludables fueron el comer mientras se emplean dispositivos de entretenimiento digital y el tiempo destinado a estos últimos.


Abstract Assessing healthy habits related to child overweight and obesity is important concerning the prevention efforts. A variety of measures to assess eating habits and physical activity are available, being the self-report frequency questionnaires the most common and cost-efficient. Nevertheless, those questionnaires generate a large amount of data. Considering this, the purpose of the study was to develop a proposal to synthesize information from the Child Overweight/Obesity Healthy related Habits Questionnaire (CHS-SO), through the creation of indexes and a combination of a factorial method and cluster analysis. Nine indexes were created to assess eating habits, physical activity, and digital entertainment use, allowing to classify children into healthy or unhealthy in each index. The CHS-SO was administered to 239 children between 8 and 12 years old from Cali, Colombia. Data obtained from the indexes were analyzed using a multiple correspondence analysis and cluster analysis. Results show that most of the children have healthy eating habits, physical activity was lower in girls and digital entertainment use was high.

18.
Thromb Haemost ; 118(9): 1668-1678, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30103252

RESUMO

International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years (ß = 80%; α one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Dalteparina/uso terapêutico , Neoplasias/tratamento farmacológico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Doença Aguda , Administração Oral , Adulto , Europa (Continente) , Seguimentos , Humanos , Neoplasias/complicações , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos , Tromboembolia Venosa/complicações
19.
Sensors (Basel) ; 18(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071647

RESUMO

Nowadays, citizens have a huge concern about the quality of life in their cities, especially regarding the level of pollution. Air quality level is of great importance, not only to plan our activities but also to take precautionary measures for our health. All levels of governments are concerned about it and have built their indexes to measure the air quality level in their countries, regions or cities. Taking into account the existing sensor infrastructure within smart cities, it makes possible to evaluate these indices and to know anywhere the level of pollution in real-time. In this scenario, the main objective of the current work is to foster citizens' awareness about pollution by offering pollution-free routes. To achieve this goal, a technology-agnostic methodology is presented, which allows for creating pollution-free routes across cities depending on the level of pollution in each zone. The current work includes an extensive study of existing air quality indices, and proposes and carries forward to deployment of the defined methodology in a big city, such as Madrid (Spain).

20.
Oncologist ; 23(11): 1271-e128, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30120161

RESUMO

LESSONS LEARNED: RAS- or BRAF-mutated metastatic colorectal cancers (mCRCs) progressing after first-line treatment have a poor prognosis.European and U.S. guidelines include the multikinase inhibitor regorafenib as a standard option for second-line therapy and beyond, based on the results of the randomized phase III CORRECT trial demonstrating improvement in survival.Although stopped prematurely for failing to accrue, the PREVIUM trial, the first prospective interventional study exploring regorafenib as second-line treatment for patients with mCRC bearing RAS or BRAF mutations, failed to demonstrate clinical activity in the population analyzed. BACKGROUND: Patients with RAS- or BRAF-mutated (mut) metastatic colorectal cancer (mCRC) progressing on first-line bevacizumab plus 5-FU/irinotecan/oxaliplatin (FOLFOXIRI) have a poor prognosis. We aimed to assess the efficacy and safety of regorafenib in this population. METHODS: Regorafenib was administered daily for 3 weeks of each 4-week cycle until disease progression or other reason. The primary endpoint was 6-month progression-free survival (PFS). RESULTS: KRAS, NRAS, or BRAF was mutated in mCRC samples in 60%, 20%, and 13% of patients, respectively. Median time from initial diagnosis of metastases to the start of regorafenib and treatment duration was 13.8 months and 7 weeks, respectively. Reasons for discontinuation included disease progression (80%), investigator decision (13%), and adverse events (AEs; 7%). Seven patients (47%) required dose reduction, mostly for asthenia (43%). The most common regorafenib-related grade 3 AEs were asthenia (33%), dysphonia (13%), and hypertension (13%) (Table 1). There were no grade 4 toxicities. No patient was progression-free at 6 months. Median PFS, time to progression (TTP), and overall survival (OS) were 2.2, 2.0, and 3.3 months, respectively. CONCLUSION: Although stopped prematurely for failing to accrue, in the population analyzed, regorafenib failed to demonstrate clinical activity in KRAS- or BRAF-mutated mCRC with progression following first-line with FOLFOXIRI plus bevacizumab, although tolerability was acceptable. Our trial suggests that exploring regorafenib efficacy in an earlier line of therapy should not be undertaken without better population refinement.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridinas/uso terapêutico , Proteínas ras/genética , Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab/farmacologia , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Masculino , Mutação , Metástase Neoplásica , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA