RESUMO
The thermodynamic formalism of nonequilibrium systems together with the theory of complex systems and systems biology offer an appropriate theoretical framework to explain the complexity observed at the macroscopic level in physiological phenomena. In turn, they allow the establishment of an appropriate conceptual and operational framework to address the study of phenomena such as the emergence and evolution of cancer.This chapter is organized as follows: In Subheading 1, an integrated vision of these disciplines is offered for the characterization of the emergence and evolution of cancer, seen as a nonlinear dynamic system, temporally and spatially self-organized out of thermodynamic equilibrium. The development of the various mathematical models and different techniques and approaches used in the characterization of cancer metastasis is presented in Subheading 2. Subheading 3 is devoted to the time course of cancer metastasis, with particular emphasis on the epithelial-mesenchymal transition (EMT henceforth) as well as chronotherapeutic treatments. In Subheading 4, models of the spatial evolution of cancer metastasis are presented. Finally, in Subheading 5, some conclusions and remarks are presented.
Assuntos
Modelos Teóricos , Neoplasias , Humanos , Termodinâmica , Neoplasias/patologia , Dinâmica não Linear , Transição Epitelial-MesenquimalRESUMO
Purslane (Portulaca oleracea L.) has a high content of nutrients and medicinal effects that depend on the genotype, harvesting time, and production system. The objective of the present research work was to elucidate the NMR-based metabolomics profiling of three native purslane cultivars from Mexico (Xochimilco, Mixquic, and Cuautla) grown under hydroponic conditions and harvested in three different times (32, 39, and 46 days after emergence). Thirty-nine metabolites identified in the 1H NMR spectra of aerial parts of purslane, 5 sugars, 15 amino acids, 8 organic acids, 3 caffeoylquinic acids, as well as 2 alcohols and 3 nucleosides, choline, O-phosphocholine and trigonelline were also detected. A total of 37 compounds were detected in native purslane from Xochimilco and Cuautla, whereas 39 compounds were detected in purslane from Mixquic. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) separated the cultivars into three clusters. Mixquic cultivar had the highest number of differential compounds (amino acids and carbohydrates), followed by Xochimilco and Cuautla cultivars, respectively. Changes in the metabolome were observed in latest times of harvest for all the cultivars studied. The differential compounds were glucose, fructose, galactose, pyruvate, choline, and 2-hydroxysobutyrate. The results obtained in this investigation may contribute to selecting the best cultivar of purslane and the best time in which the levels of nutrients are optimal.
Assuntos
Portulaca , Portulaca/química , Hidroponia , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Aminoácidos/análiseRESUMO
BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Feminino , Adulto , Masculino , COVID-19/epidemiologia , Colômbia/epidemiologia , Estudos Soroepidemiológicos , Estudos Transversais , Imunoglobulina G , Pessoal de Saúde , Recursos Humanos em Hospital , HospitaisRESUMO
BACKGROUND: The use of rosuvastatin plus colchicine and emtricitabine/tenofovir in hospitalized patients with SARS-CoV-2 disease (COVID-19) has not been assessed. The objective of this study was to assess the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir, and their combined use in these patients. METHODS: This was a randomized, controlled, open-label, multicentre, parallel, pragmatic study conducted in six referral hospitals in Bogotá, Colombia. The study enrolled hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 complicated with pneumonia, not on chronic treatment with the study medications, and with no contraindications for their use. Patients were assigned 1:1:1:1. 1) emtricitabine with tenofovir disoproxil fumarate (FTC/TDF, 200/300 mg given orally for 10 days); 2) colchicine plus rosuvastatin (COLCH+ROSU, 0.5 mg and 40 mg given orally for 14 days); 3) emtricitabine with tenofovir disoproxil plus colchicine and rosuvastatin at the same doses and for the same period of time (FTC/TDF+COLCH+ROSU); or 4) the Colombian consensus standard of care, including a corticosteroid (SOC). The primary endpoint was 28-day all-cause mortality. A modified intention-to-treat analysis was used together with a usefulness analysis to determine which could be the best treatment. The trial was registered at ClinicalTrials.gov: NCT04359095. FINDINGS: Out of 994 candidates considered between August 2020 and March 2021, 649 (65.3%) patients agreed to participate and were enrolled in this study; among them, 633 (97.5%) were included in the analysis. The mean age was 55.4 years (SD ± 12.8 years), and 428 (68%) were men; 28-day mortality was significantly lower in the FTC/TDF+COLCH+ROSUV group than in the SOC group, 10.7% (17/159) vs. 17.4% (28/161) (hazard ratio [HR] 0.53; 95% CI 0.29 to 0.96). Mortality in the FTC/TDF group was 13.8% (22/160, HR 0.68, 95% CI 0.39 to 1.20) and 14.4% in the COLCH+ROSU group (22/153) (HR 0.78, 95% CI 0.44 to 1.36). A lower need for invasive mechanical ventilation was observed in the FTC/TDF+COLCH+ROSUV group than in the SOC group (risk difference [RD] - 0.08, 95% CI 0.11 to 0.04). Three patients presented severe adverse events, one severe diarrhoea in the COLCH+ROSU and one in the FTC/TDF+COLCH+ROSU group and one general exanthema in the FTC/TDF group. INTERPRETATION: The combined use of FTC/TDF+COLCH+ROSU reduces the risk of 28-day mortality and the need for invasive mechanical ventilation in hospitalized patients with pulmonary compromise from COVID-19. More randomized controlled trials are needed to compare the effectiveness and cost of treatment with this combination versus other drugs that have been shown to reduce mortality from SARS-CoV-2 infection and its usefulness in patients with chronic statin use.
RESUMO
OBJECTIVE: To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. RESULTS: Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-diameter and Sylvian-fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation, with complete overlap of the mean gestational age and 95% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. CONCLUSION: We present, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Cerebelo/embriologia , Aqueduto do Mesencéfalo/embriologia , Desenvolvimento Fetal , Gráficos de Crescimento , Ultrassonografia Pré-Natal , Adulto , Brasil , Cerebelo/crescimento & desenvolvimento , Aqueduto do Mesencéfalo/crescimento & desenvolvimento , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Índia , Lactente , Recém-Nascido , Itália , Quênia , Estudos Longitudinais , Masculino , Gravidez , Resultado da Gravidez , Padrões de Referência , Reino UnidoRESUMO
BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.
Assuntos
Doença de Chagas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/isolamento & purificação , Adulto , Assistência ao Convalescente , Argentina/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/parasitologia , Doença Crônica , Colômbia/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Nitroimidazóis/farmacocinética , Carga Parasitária/estatística & dados numéricos , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Tripanossomicidas/farmacocinética , Trypanosoma cruzi/genéticaRESUMO
Aegilips chilensis Bréthes, 1918 is redescribed and illustrated. Aegilips chilensis is considered an endemic species of the Andean region, characterized for having anteroposterior cephalic processes, resembling spines, formed from the postgenal carina. This and other diagnostic characters are diagnosed and illustrated, and morphological affinities of Aegilips Haliday, 1835 with other Anacharitinae genera are discussed. Redescription and photographs of Aegilips chilensis are given.
Assuntos
Himenópteros/anatomia & histologia , Himenópteros/classificação , Animais , Argentina , Chile , Feminino , MasculinoRESUMO
La afectación ovárica como debut de un linfoma de Burkitt sin enfermedad extraovárica detectable es anecdótica, por lo que habitualmente no se incluye como hipótesis diagnóstica tras el hallazgo de una tumoración ovárica. Su desconocimiento lleva a realizar un tratamiento equivocado que puede llegar a comprometer el deseo reproductivo de la paciente. Presentamos el caso de una paciente que presenta un linfoma de Burkitt con afectación ovárica como manifestación inicial. La paciente desarrolló una progresión sistemática excepcionalmente rápida. A propósito de este caso y de su inusual evolución, revisamos la literatura existente.
Ovarian involvement as the initial manifestation of a Burkitt lymphoma without detectable extra-ovarian disease is rare, which is why it is usually not included in the differential diagnosis when an ovarian tumor is detected. A missed diagnosis will lead to the wrong treatment being given, and this can compromise any future reproductive wishes of the patient. In this article, a patient presents a Burkitt lymphoma with ovarian involvement as an initial manifestation and an unusually rapid systemic progression of the disease. Prompted by this case and its unusual course, we reviewed the existing literature.
Assuntos
Humanos , Feminino , Adolescente , Neoplasias Ovarianas/diagnóstico , Linfoma de Burkitt/diagnóstico , Neoplasias Ovarianas/patologia , Linfoma de Burkitt/patologia , Progressão da Doença , Diagnóstico DiferencialRESUMO
The calculation of absolute binding affinities for protein-inhibitor complexes remains as one of the main challenges in computational structure-based ligand design. The present work explored the calculations of surface fractal dimension (as a measure of surface roughness) and the relationship with experimental binding free energies of Plasmepsin II complexes. Plasmepsin II is an attractive target for novel therapeutic compounds to treat malaria. However, the structural flexibility of this enzyme is a drawback when searching for specific inhibitors. Concerning that, we performed separate explicitly solvated molecular dynamics simulations using the available high-resolution crystal structures of different Plasmepsin II complexes. Molecular dynamics simulations allowed a better approximation to systems dynamics and, therefore, a more reliable estimation of surface roughness. This constitutes a novel approximation in order to obtain more realistic values of fractal dimension, because previous works considered only x-ray structures. Binding site fractal dimension was calculated considering the ensemble of structures generated at different simulation times. A linear relationship between binding site fractal dimension and experimental binding free energies of the complexes was observed within 20 ns. Previous studies of the subject did not uncover this relationship. Regression model, coined FD model, was built to estimate binding free energies from binding site fractal dimension values. Leave-one-out cross-validation showed that our model reproduced accurately the absolute binding free energies for our training set (R2 = 0.76; <|error|> =0.55 kcal/mol; SDerror = 0.19 kcal/mol). The fact that such a simple model may be applied raises some questions that are addressed in the article.
Assuntos
Ácido Aspártico Endopeptidases/química , Proteínas de Protozoários/química , Domínio Catalítico , Entropia , Fractais , Ligantes , Simulação de Dinâmica Molecular , Ligação Proteica , Propriedades de Superfície , TermodinâmicaRESUMO
Cosmopolitan pests such as Brevicoryne brassicae, Lipaphis pseudobrassicae, and Myzus persicae (Aphididae) cause significant damage to Brassicaceae crops. Assessment of the important biotic and abiotic factors that regulate these pests is an essential step in the development of effective Integrated Pest Management programs for these aphids. This study evaluated the influence of leaf position, precipitation, temperature, and parasitism on populations of L. pseudobrassicae, M. persicae, and B. brassicae in collard greens fields in the Triângulo Mineiro region (Minas Gerais state), Brazil. Similar numbers of B. brassicae were found on all parts of the collard green plants, whereas M. persicae and L. pseudobrassicae were found in greatest numbers on the middle and lower parts of the plant. While temperature and precipitation were positively related to aphid population size, their effects were not accumulative, as indicated by a negative interaction term. Although Diaeretiella rapae was the main parasitoid of these aphids, hyperparasitism was dominant; the main hyperparasitoid species recovered from plant samples was Alloxysta fuscicornis. Parasitoids seem to have similar distributions on plants as their hosts. These results may help predict aphid outbreaks and gives clues for specific intra-plant locations when searching for and monitoring aphid populations.