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Dengue disease transmission is a complex vector-borne disease, mainly due to the co-circulation of four serotypes of the virus. Mathematical models have proved to be a useful tool to understand the complexity of this disease. In this work, we extend the model studied by Esteva et al., 2003, originally proposed for two serotypes, to four circulating serotypes. Using epidemic data of dengue fever in Iquitos (Peru) and San Juan (Puerto Rico), we estimate numerically the co-circulation parameter values for selected outbreaks using a bootstrap method, and we also obtained the Basic Reproduction Number, R0, for each serotype, using both analytical calculations and numerical simulations. Our results indicate that the impact of co-circulation of serotypes in population dynamics of dengue infection is such that there is a reduced effect from DENV-3 to DENV-4 in comparison to no-cross effect for epidemics in Iquitos. Concerning San Juan epidemics, also comparing to no-cross effect, we also observed a reduced effect from the predominant serotype DENV-3 to both DENV-2 and DENV-1 epidemics neglecting the very small number of cases of DENV-4.
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Vírus da Dengue , Dengue , Epidemias , Humanos , Surtos de Doenças , SorogrupoRESUMO
Introduction: Drug-related problems (DRP) are events or circumstances in which drug therapy does or could interfere with desired health outcomes. In December 2019, a new coronavirus, SARS-CoV-2, appeared. Little knowledge about this type of infection resulted in the administration of various drugs with limited use in other pathologies. Evidence about DRP in patients with COVID-19 is lacking. Objective: The aim of the present study is to describe identified cases of DRP and those drugs involved in the first wave of patients with COVID-19, and evaluate associated risk factors. Material and methods: Observational, retrospective study performed in a tertiary university hospital between 14th March 2020 and 31 May 2020 (corresponding to the first COVID-19 wave). We recruited patients admitted during the study period. Exclusion criteria included age < 18 years; admission to critically ill units; and care received either in the emergency room, at-home hospitalization or a healthcare center. Results: A total of 817 patients were included. The mean age was 62.5 years (SD 16.4) (range 18-97), and 453 (55.4%) were male. A total of 516 DRP were detected. Among the patients, 271 (33.2%) presented at least one DRP. The mean DRP per patient with an identified case was 1.9. The prevailing DRPs among those observed were: incorrect dosage (over or underdosage) in 145 patients (28.2%); wrong drug combination in 131 (25.5%); prescriptions not in adherence to the then COVID-19 treatment protocol in 73 (14.1%); prescription errors due to the wrong use of the computerized physician order entry in 47 (9.2%); and incorrect dosage due to renal function in 36 (7%). The logistic regression analysis showed that patients who received only prescriptions of antibacterials for systemic use (J01 ATC group) faced a higher likelihood of experiencing a DRP (OR 2.408 (1.071-5.411), p = 0.033). Conclusion: We identified several factors associated with an increased risk of DRPs, similar to those reported in other pre-pandemic studies, including a prolonged length of stay, higher number of prescribed drugs and antimicrobial administration. The relevance of pharmacists and tools like pharmacy warning systems can help prevent, identify and resolve DRP efficiently.
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BACKGROUND: Benznidazole and nifurtimox are effective drugs used to treat Chagas' disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs. OBJECTIVES: To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice. METHODS: Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times. RESULTS: Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model. CONCLUSIONS: In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas' disease.
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Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Animais , Doença de Chagas/tratamento farmacológico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Nicarágua , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêuticoRESUMO
In the published article, the following information was missing.
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BACKGROUND: The development of a safe and effective vaccine is considered crucial for dengue transmission control since vetor control has been failed; some potential candidates are currently in test, and in this context theoretical studies are necessary to evaluate vaccination strategies such as the age groups that should be vaccinated, the percentage of the population at risk, and the target geographic regions to make dengue control feasible and optimal. METHODS: A partial differential model is used to mimics dengue transmission in human population in order to estimate the optimal vaccination age, using data collected from dengue reported cases in ten cities of Brazil from 2001 to 2014. For this purpose, the basic reproduction number of the disease was minimized assuming a single-dose vaccination strategy, equal vaccine efficacy for all circulating serotypes, and no vaccine failure. Numerical methods were used to assess the optimal vaccination age and its confidence age range. RESULTS: The results reveal complex spatial-temporal patterns associated to the disease transmission, highlighting the heterogeneity in defining the target population for dengue vaccination. However, the values obtained for the optimal age of vaccination, as targeting individuals under 13 years old, are compatible with the ones reported in similar studies in Brazil. The results also show that the optimal age for vaccination in general does not match with the age of the highest number of cases. CONCLUSIONS: The variation of the optimal age for vaccination across the country reflects heterogeneities in dengue spatial-temporal transmission in Brazilian cities, and can be used to define the target population and cities to optimize vaccination strategies in a context of high cost and low quantity of available vaccine.
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Vacinas contra Dengue/administração & dosagem , Dengue/prevenção & controle , Dengue/transmissão , Vacinação/métodos , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Criança , Pré-Escolar , Cidades , Dengue/epidemiologia , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Modelos Teóricos , Análise Espaço-Temporal , Adulto JovemRESUMO
Colorectal cancer (CRC) is one of the tumours with the highest incidence and mortality in the Spanish population. Nevertheless, the advances in prevention and treatment have contributed to an increased number of patients who survive for prolonged periods of time. In addition, despite recurrences, improved survival following metastasis resection is likewise on the rise. This underscores the importance of carrying out follow-up programmes even in low-risk patients for the early detection of recurrence. The main objective of this article is to provide a set of recommendations for optimising the follow-up of CRC survivors as well as for managing the sequelae that result from either pharmacological or surgical treatment.
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Sobreviventes de Câncer , Neoplasias do Colo/diagnóstico , Continuidade da Assistência ao Paciente , Recidiva Local de Neoplasia/diagnóstico , Vigilância da População , Neoplasias Retais/diagnóstico , Antineoplásicos/efeitos adversos , Antígeno Carcinoembrionário/análise , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Colonoscopia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Oxaliplatina/efeitos adversos , Equipe de Assistência ao Paciente , Complicações Pós-Operatórias , Prevenção Primária , Radioterapia/efeitos adversos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Prevenção Secundária , Disfunções Sexuais Fisiológicas/etiologia , Fatores de TempoRESUMO
OBJECTIVE: The aim of our study was to determine the self-reported prevalence of use of emergency contraception (EC), identify factors associated with EC use, and measure the prevalence in university students of pregnancy and abortion among users and non-users of EC. METHODS: A cross-sectional descriptive study of university students using a self-administered questionnaire was carried out in 2016. The main dependent variable was EC use at any time. Independent variables included sociodemographic factors and factors related to harmful habits and sexual behaviour. RESULTS: The study sample consisted of 1309 students (median age 20 years). Forty per cent of participants reported using EC; condom failure was given as the main reason. Variables associated with EC use in both men and women were illegal drug consumption and having had more than 10 sexual partners. In women, other factors associated with EC use were age at first coitus and non-centrist political views. The prevalence of pregnancy was 6.5% and the prevalence of voluntary abortion was 2.9%. This prevalence was similar for men and women and for EC users and non-users. CONCLUSION: EC use in university students was more likely in those who experienced contraceptive failure or used no contraception. There were differences between men and women. Those at higher risk of unplanned pregnancy were more likely to report EC use, which may explain why there was no difference in the rates of unwanted pregnancies between EC users and non-users.
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Comportamento Contraceptivo/estatística & dados numéricos , Anticoncepção Pós-Coito/estatística & dados numéricos , Assunção de Riscos , Comportamento Sexual/psicologia , Preservativos/efeitos adversos , Comportamento Contraceptivo/psicologia , Anticoncepção Pós-Coito/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Gravidez , Gravidez não Planejada/psicologia , Prevalência , Fatores de Risco , Estudantes , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
BACKGROUND: Emergency contraception (EC) is an effective postcoital contraceptive method for reducing the risk of unwanted pregnancy after unprotected intercourse. The estimated effectiveness of EC is between 70 and 89% if taken within 72 h following intercourse. Most of the studies carried out in Spain are quantitative and from the perspective of health professionals. In this study, we intend to explore the knowledge of, attitudes towards and discourse regarding the use of EC in women aged 15 to 25 years. METHODS: Sample: A qualitative study including in-depth interviews with 19 women between 15 and 25 years of age was performed. INCLUSION CRITERIA: Participants were natives of Spain or of a Latin American country. Segmentation criteria: Participants had experience in the use of EC. DATA COLLECTION: Participants were selected by health care informants and by the snowball technique among university students. DATA ANALYSIS: A thematic analysis was performed. Preliminary analyses were made during the course of the field work to adapt the script and to assess data saturation. A preliminary code tree was developed by two researchers, and the coding of the text was done with the Atlas.ti 5.0 software. RESULTS: EC is perceived positively by women. They do not express issues with taking it, although some feel guilty. The reason for taking EC is to avoid unwanted pregnancy and abortion. Women also feel that EC should be used in moderation. False beliefs and misconceptions regarding EC are held: EC delivers an excess of hormones, induces abortion and causes severe side effects. Women mention that the health professionals who provide EC have moral beliefs. Women use it because of condom breakage associated with their first coital relations. CONCLUSIONS: The results of this study have public health implications: The sexual-affective health education received by young people should incorporate clear information about the mechanism of action of the EC pill and its side effects together with empowerment strategies addressing guilt and moralistic messages. Programmes and training activities for health professionals must be designed to prevent the communication of inappropriate messages such as those that exaggerate the side effects of EC and those that promote fear and guilt, because they represent a barrier to the responsible use of this medication.
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Anticoncepção Pós-Coito , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Feminino , Humanos , Pesquisa Qualitativa , Espanha , Adulto JovemRESUMO
BACKGROUND: The benefits from expedited diagnosis of symptomatic cancer are uncertain. We aimed to analyse the relationship between stage of colorectal cancer (CRC) and the primary and specialist care components of the diagnostic interval. METHODS: We identified seven independent data sets from population-based studies in Scotland, England, Canada, Denmark and Spain during 1997-2010 with a total of 11 720 newly diagnosed CRC patients, who had initially presented with symptoms to a primary care physician. Data were extracted from patient records, registries, audits and questionnaires, respectively. Data sets were required to hold information on dates in the diagnostic interval (defined as the time from the first presentation of symptoms in primary care until the date of diagnosis), symptoms at first presentation in primary care, route of referral, gender, age and histologically confirmed stage. We carried out reanalysis of all individual data sets and, using the same method, analysed a pooled individual patient data set. RESULTS: The association between intervals and stage was similar in the individual and combined data set. There was a statistically significant convex (â©-shaped) association between primary care interval and diagnosis of advanced (i.e., distant or regional) rather than localised CRC (P=0.004), with odds beginning to increase from the first day on and peaking at 90 days. For specialist care, we saw an opposite and statistically significant concave (âª-shaped) association, with a trough at 60 days, between the interval and diagnosis of advanced CRC (P<0.001). CONCLUSIONS: This study provides evidence that longer diagnostic intervals are associated with more advanced CRC. Furthermore, the study cannot define a specific 'safe' waiting time as the length of the primary care interval appears to have negative impact from day one.
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Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Diagnóstico Tardio , Detecção Precoce de Câncer , Atenção Primária à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Estudos de Coortes , Conjuntos de Dados como Assunto , Dinamarca , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Escócia , Espanha , Avaliação de Sintomas , Fatores de TempoRESUMO
In Spain, as around the world, the number of cancer survivors is increasing. There were an estimated 500,000 cancer survivors in 2010. In spite of recognition that Survivorship Care Plans (SCPs) are needed, their implementation in Spain has been slower than in other countries and only in very recent years some small initiatives have been carried out. This editorial addresses the difficulties to implement SCPs in the Spanish Health Services and which are the opportunities that favour a scenario in which PCPs and oncologists can offer a real patient-centred care to cancer survivors.
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Neoplasias/terapia , Sobrevivência , Atenção à Saúde/organização & administração , Humanos , Avaliação das Necessidades , Planejamento de Assistência ao Paciente/organização & administração , Espanha , Sobreviventes/estatística & dados numéricosRESUMO
OBJECTIVES: To establish cause-specific survival by stage of colorectal cancer up to 8 years from diagnosis, and to identify factors which explain and predict the likelihood of survival. METHODOLOGY: Retrospective follow-up study of people diagnosed with invasive colorectal cancer during 2006-2011, identified through the Mallorca Cancer Registry. DCO and lymphomas were excluded. Sex, age, diagnostic method, site, histology, T, N, M, and stage, date of diagnosis, date of follow-up or death, and cause of death were collected. End point of follow-up was 31st December 2013. Multiple imputation (MI) method was performed to obtain stage when unknown. Actuarial and Kaplan-Meier methods were used for survival analysis. Extended Cox models were built to identify factors that explain and predict survival. RESULTS: 2889 cases were identified, 41.7% in women and 58.3% in men, with a mean age of 70.5 years. Unknown stage represented 15.3% of cases. After MI, 15% were in stage I, 26.7% were in II, 32.7% in III, and 25.6% in IV. Survival was 56% at the end of the 5th year. Survival by stage changed significantly after MI and was estimated to 83% at stage I, 73% at II, 62% at III, and 16% at IV. Extended Cox model showed that survival worsened with age, mucinous histology, and stage. Risk of dying was 17.0 times higher in stage IV compared to stage I, 3.7 times in stage III, and 1.6 times in stage II. CONCLUSIONS: More than half of colorectal cancer patients will survive 5 years after diagnosis, but only if diagnosed in stages I-III.
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Neoplasias Colorretais/patologia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espanha/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
PURPOSE: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. METHODS: Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. RESULTS: Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. CONCLUSIONS: The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology.
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Técnicas Histológicas/métodos , Imageamento por Ressonância Magnética/métodos , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Atlas como Assunto , Contagem de Células , Fixadores , Formaldeído , Géis , Humanos , Imageamento Tridimensional , Masculino , Microtomia , Pessoa de Meia-Idade , Prostatectomia , SefaroseRESUMO
The thermal conductivity, specific heat, and specific volume of the orientational glass former 1,1,2-trichloro-1,2,2-trifluoroethane (CCl2F-CClF2, F-113) have been measured under equilibrium pressure within the low-temperature range, showing thermodynamic anomalies at ca. 120, 72, and 20 K. The results are discussed together with those pertaining to the structurally related 1,1,2,2-tetrachloro-1,2-difluoroethane (CCl2F-CCl2F, F-112), which also shows anomalies at 130, 90, and 60 K. The rich phase behavior of these compounds can be accounted for by the interplay between several of their degrees of freedom. The arrest of the degrees of freedom corresponding to the internal molecular rotation, responsible for the existence of two energetically distinct isomers, and the overall molecular orientation, source of the characteristic orientational disorder of plastic phases, can explain the anomalies at higher and intermediate temperatures, respectively. The soft-potential model has been used as the framework to describe the thermal properties at low temperatures. We show that the low-temperature anomaly of the compounds corresponds to a secondary relaxation, which can be associated with the appearance of Umklapp processes, i.e., anharmonic phonon-phonon scattering, that dominate thermal transport in that temperature range.
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BACKGROUND: Benzodiazepines are extensively used in primary care, but their long-term use is associated with adverse health outcomes and dependence. AIMS: To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use. METHOD: A multicentre three-arm cluster randomised controlled trial was conducted, with randomisation at general practitioner level (trial registration ISRCTN13024375). A total of 532 patients taking benzodiazepines for at least 6 months participated. After all patients were included, general practitioners were randomly allocated (1:1:1) to usual care, a structured intervention with follow-up visits (SIF) or a structured intervention with written instructions (SIW). The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription claims at 12 months. RESULTS: At 12 months, 76 of 168 (45%) patients in the SIW group and 86 of 191 (45%) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 (15%) in the control group. After adjusting by cluster, the relative risks for benzodiazepine discontinuation were 3.01 (95% CI 2.03-4.46, P<0.0001) in the SIW and 3.00 (95% CI 2.04-4.40, P<0.0001) in the SIF group. The most frequently reported withdrawal symptoms were insomnia, anxiety and irritability. CONCLUSIONS: Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity. A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits.
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Benzodiazepinas/efeitos adversos , Educação de Pacientes como Assunto/métodos , Atenção Primária à Saúde/métodos , Síndrome de Abstinência a Substâncias/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/terapia , Idoso , Análise por Conglomerados , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Espanha , Resultado do TratamentoRESUMO
The determination of the molecular ordering in a liquid is still a controversial subject. There is no general consensus either on the methods to obtain reliable liquid structures or on the way to analyze them. Regardless of the method, it is very important to have a realistic molecular structure available that allows simulations to faithfully reproduce the sample features, and that minimizes the computing time in structure refinements. However, attention is not always paid to this point and molecular models coming from general force-fields are frequently used to undertake many of the analyses. We propose in this work to use a Bayesian scheme to fit the experimental data and produce reliable molecular models that can be used as the starting point of any simulation or refinement. The algorithm behind the proposed method is based on a Markov chain Monte Carlo procedure, as many other refinement programs such as reverse Monte Carlo or empirical potential structure refinement.
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Sulphoglycosphingolipids, present on the surface of diverse cells, participate in the regulation of various cellular events. However, little is known about the structure and the role of sulphoglycosphingolipids in trypanosomatids. Herein, sulphated dihexosylceramide structures - composed mainly of sphingosine as the long chain base acylated with stearic acid - have been determined for the first time in Trypanosoma cruzi epimastigotes by UV-MALDI-TOF-MS analysis. Interestingly, inhibition ELISA assays using cruzipain as antigen and polyclonal rabbit antibodies specific for cruzipain, the major cysteine proteinase of T. cruzi, or for its C-terminal domain, have demonstrated (i) that sulphate epitopes are shared between cruzipain and sulphatides of T. cruzi, (ii) that cross-reactivity maps to the C-terminal domain and (iii) the existence of other antigenic determinants in the glycolipidic structures. These features provide evidence that sulphate groups are antigenic in sulphate-containing parasite glycoconjugates. Furthermore, IgG2 antibody levels inversely correlate with disease severity in chronic Chagas disease patients, suggesting that IgG2 antibodies specific for sulphated epitopes might be associated with protective immunity and might be considered as potential surrogates of the course of chronic Chagas disease.
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Glicoconjugados/análise , Glicoconjugados/imunologia , Sulfoglicoesfingolipídeos/análise , Sulfoglicoesfingolipídeos/imunologia , Trypanosoma cruzi/química , Trypanosoma cruzi/imunologia , Adulto , Animais , Antiprotozoários/sangue , Doença de Chagas/imunologia , Reações Cruzadas , Cisteína Endopeptidases/química , Cisteína Endopeptidases/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Proteínas de Protozoários , Coelhos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Trans-1,2-dichloroethene (HClC=CClH) has several structural and dynamic anomalies between its low- and high-density liquid, previously found through neutron scattering experiments. To explain the microscopic origin of the differences found in those experiments, a series of molecular dynamics simulations were performed. The analysis of molecular short-range order shows that the number of molecules in the first neighbor shell is 12 for the high-density liquid and 11 for the low-density one. It also shows that the angular position of the center of mass of the first neighbor is roughly the same although the molecular orientation is not. In both liquids the first neighbor and its reference molecule arrange mainly in two configurations, each being the most probable in one of the liquids. First neighbors in the configuration that predominates in the high-density liquid tend to locate themselves closer to the reference molecule, an evidence that they are more strongly bonded. This arrangement facilitates a better packing of the rest of molecules in the first neighbor shell so that on average an additional molecule can be included, and is proposed to be the key in the explanation of all the observed anomalies in the characteristics of both liquids.
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Dicloroetilenos/química , Simulação de Dinâmica Molecular , Água/química , Ligação de Hidrogênio , Modelos Moleculares , TermodinâmicaRESUMO
Fitting a data set with a parametrized model can be seen geometrically as finding the global minimum of the χ(2) hypersurface, depending on a set of parameters {P(i)}. This is usually done using the Levenberg-Marquardt algorithm. The main drawback of this algorithm is that despite its fast convergence, it can get stuck if the parameters are not initialized close to the final solution. We propose a modification of the Metropolis algorithm introducing a parameter step tuning that optimizes the sampling of parameter space. The ability of the parameter tuning algorithm together with simulated annealing to find the global χ(2) hypersurface minimum, jumping across χ(2){P(i)} barriers when necessary, is demonstrated with synthetic functions and with real data.
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Single units of O-linked N-acetylglucosamine (GlcNAc), usually components of nuclear and cytoplasmatic proteins, are present at the C-terminal domain of cruzipain (Cz), a lysosomal major antigen from Trypanosoma cruzi. On the other hand, antibodies directed against some self-antigens like myosin are associated with Chagas heart disease. The participation of O-GlcNAc moieties in the molecular antigenicity of Cz was determined using GlcNAc linked to aprotinin by ELISA. The immune cross-reactivity between Cz and myosin is mainly focused in the C-T domain. ELISA inhibition assays using rabbit sera specific for Cz and C-T in conjunction with immune-gold electron microscopy analysis of heart tissues from mice immunized with C-T confronted with polyclonal rabbit sera specific for Cz and C-T prior and after myosin adsorption provided evidence which indicates that O-GlcNAc moieties constitute a common epitope between Cz and either myosin or other cardiac O-GlcNAc-containing proteins, showing a new insight into the molecular immune pathogenesis of Chagas heart disease.
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Acetilglucosamina/imunologia , Anticorpos Antiprotozoários/imunologia , Reações Cruzadas , Cisteína Endopeptidases/imunologia , Epitopos/imunologia , Miosinas/imunologia , Trypanosoma cruzi/imunologia , Acetilglucosamina/análise , Animais , Cisteína Endopeptidases/química , Ensaio de Imunoadsorção Enzimática , Epitopos/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Imunoeletrônica , Miocárdio/patologia , Miosinas/química , Proteínas de Protozoários , Coelhos , Trypanosoma cruzi/químicaRESUMO
This study aims to find out how the presenting symptoms of colorectal cancer are interpreted by those who get them, to identify the main triggering factors that lead someone with colorectal cancer symptoms to consult a doctor, and to describe how those affected perceive the process of being diagnosed with colorectal cancer. It is a qualitative study performed within the theoretical framework of symbolic interactionism and from a gender perspective. Grounded theory has been used for the analysis. Semi-structured interviews were conducted. Twelve individuals with colorectal cancer - seven men and five women - were interviewed. At first, both the men and women attributed their symptoms to trivial causes. Changes in symptoms or the persistence of symptoms trigger medical consultation. Close relatives, especially the closest female family members, can trigger medical consultation, particularly among men. The women said nothing to their families until they had already gone to the doctor. Knowledge about colorectal cancer could be a factor triggering medical consultation. The time between consulting the family doctor and seeing a specialist feels drawn out. Gender-related differences have been observed in respect to help-seeking in colorectal cancer. Health education programmes focusing on knowledge about cancer are needed.