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We investigated decays of ^{51,52,53}K at the ISOLDE Decay Station at CERN in order to understand the mechanism of the ß-delayed neutron-emission (ßn) process. The experiment quantified neutron and γ-ray emission paths for each precursor. We used this information to test the hypothesis, first formulated by Bohr in 1939, that neutrons in the ßn process originate from the structureless "compound nucleus." The data are consistent with this postulate for most of the observed decay paths. The agreement, however, is surprising because the compound-nucleus stage should not be achieved in the studied ß decay due to insufficient excitation energy and level densities in the neutron emitter. In the ^{53}K ßn decay, we found a preferential population of the first excited state in ^{52}Ca that contradicted Bohr's hypothesis. The latter was interpreted as evidence for direct neutron emission sensitive to the structure of the neutron-unbound state. We propose that the observed nonstatistical neutron emission proceeds through the coupling with nearby doorway states that have large neutron-emission probabilities. The appearance of "compound-nucleus" decay is caused by the aggregated small contributions of multiple doorway states at higher excitation energy.
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BACKGROUND: In 2014 approximately 21,200 patients were diagnosed with oesophageal and gastric cancer in England and Wales, of whom 37 % underwent planned curative treatments. Potentially curative surgical resection is associated with significant morbidity and mortality. For operable locally advanced disease, neoadjuvant chemotherapy (NAC) improves survival over surgery alone. However, NAC carries the risk of toxicity and is associated with a decrease in physical fitness, which may in turn influence subsequent clinical outcome. Lower levels of physical fitness are associated with worse outcome following major surgery in general and Upper Gastrointestinal Surgery (UGI) surgery in particular. Cardiopulmonary exercise testing (CPET) provides an objective assessment of physical fitness. The aim of this study is to test the hypothesis that NAC prior to upper gastrointestinal cancer surgery is associated with a decrease in physical fitness and that the magnitude of the change in physical fitness will predict mortality 1 year following surgery. METHODS: This study is a multi-centre, prospective, blinded, observational cohort study of participants with oesophageal and gastric cancer scheduled for neoadjuvant cancer treatment (chemo- and chemoradiotherapy) and surgery. The primary endpoints are physical fitness (oxygen uptake at lactate threshold measured using CPET) and 1-year mortality following surgery; secondary endpoints include post-operative morbidity (Post-Operative Morbidity Survey (POMS)) 5 days after surgery and patient related quality of life (EQ-5D-5 L). DISCUSSION: The principal benefits of this study, if the underlying hypothesis is correct, will be to facilitate better selection of treatments (e.g. NAC, Surgery) in patients with oesophageal or gastric cancer. It may also be possible to develop new treatments to reduce the effects of neoadjuvant cancer treatment on physical fitness. These results will contribute to the design of a large, multi-centre trial to determine whether an in-hospital exercise-training programme that increases physical fitness leads to improved overall survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325883 - 29(th) March 2011.
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Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Neoplasias Gastrointestinais/terapia , Aptidão Física/fisiologia , Inglaterra , Teste de Esforço/métodos , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento , País de GalesRESUMO
Diversity within the innate and adaptive immune response to hepatitis C is important in determining spontaneous resolution (SR) and treatment response. The aim of this study was to analyze how these variables interact in combination; furthering our understanding of the mechanisms that drive successful immunological clearance. Multivariate analysis was performed on retrospectively collected data for 357 patients previously genotyped for interferon (IFN)-λ3/4, killer cell immunoglobulin (KIR), human leukocyte antigen (HLA) class I and II and tapasin. High resolution KIR genotyping was performed for individuals with chronic infection and haplotypes determined. Outcomes for SR, IFN response and cirrhosis were examined. Statistical analysis included univariate methods, χ(2) test for trend, multivariate logistic regression, synergy and principal component analysis (PCA). Although KIR2DL3:HLA-C1C1 (P = 0.027), IFN-λ3/4 rs12979860 CC (P = 0.027), tapasin G in individuals with aspartate at residue 114 of HLA-B (TapG:HLA-B(114D) ) (P = 0.007) and HLA-DRB1*04:01 (P = 0.014) were associated with SR with a strong additive influence (χ(2) test for trend P < 0.0001); favorable polymorphisms did not interact synergistically, nor did patients cluster by outcome. In the treatment cohort, IFN-λ3/4 rs12979860 CC was protective in hepatitis C virus (HCV) G1 infection and KIR2DL3:HLA-C1 in HCV G2/3. In common with SR, variables did not interact synergistically. Polymorphisms predictive of viral clearance did not predict disease progression. In summary, different individuals resolve HCV infection using discrete and non-interacting immunological pathways. These pathways are influenced by viral genotype. This work provides novel insights into the complexity of the interaction between host and viral factors in determining the outcome of HCV infection.
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Epistasia Genética/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/genética , Interações Hospedeiro-Patógeno/genética , Cirrose Hepática/genética , Progressão da Doença , Expressão Gênica , Heterogeneidade Genética , Genótipo , Hepacivirus/patogenicidade , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferons , Interleucinas/genética , Interleucinas/imunologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Modelos Logísticos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/imunologia , Análise Multivariada , Prognóstico , Receptores KIR/genética , Receptores KIR/imunologia , Remissão Espontânea , Estudos RetrospectivosRESUMO
Interstitial deletions of chromosome 3p14p12 are a rare chromosome rearrangement. Twenty-six patients have been reported in the literature to date, however, a specific clinical phenotype has not yet been delineated. We describe three patients (two new) with overlapping chromosome 3p14p12 deletions and review the clinical and molecular data of 11 well-characterized, published cases. These patients had a number of features in common, such as short stature, failure to thrive, facial dysmorphism, congenital heart defects, urogenital abnormalities, neurological problems, hearing loss, and global developmental delay, suggesting that the interstitial chromosome 3p14p12 deletion gives rise to a multiple congenital anomaly syndrome. Some of the patients show clinical overlap with other complex syndromes such as CHARGE syndrome. Genotype-phenotype analysis revealed candidate genes for parts of the clinical features suggesting that the 3p14 deletion is a contiguous gene syndrome.
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Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 3/química , Deficiências do Desenvolvimento/genética , Anormalidades Múltiplas/patologia , Criança , Pré-Escolar , Mapeamento Cromossômico , Deficiências do Desenvolvimento/patologia , Feminino , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Índice de Gravidade de Doença , SíndromeRESUMO
Multicomponent cyclicity in influenza (flu) incidence had been observed in various countries (e.g. periods T = 1, 2-3, 5-6, 8·0, 10·6-11·3, 13, 18-19 years) and its close similarity with cycles in natural environmental phenomena as meteorological factors and heliogeophysical activity (HGA) suggested. This report aimed at verifying previous results on cyclic patterns of flu incidence by exploring whether flu annual cyclicity (seasonality) and trans-year (13 to <24 months) and/or multiannual (long-term, ⩾24 months) cycles might be present. For this purpose, a relatively long monthly flu incidence dataset consisting of absolute numbers of new cases from the Grand Baku area, Azerbaijan, for the years 1976-2000 (300 months) was analysed. The exploration of underlying chronomes or, time structures, was done by linear and nonlinear parametric regression models, autocorrelation, spectral analysis and periodogram regression analysis. We analysed temporal dynamics and described multicomponent cyclicity, determining its statistical significance. The analysis, considering the flu data specifically stratified in three distinct intervals (1976-1990, 1991-1995, 1996-2000), and also combinations thereof, indicated that the main cyclic pattern was a seasonal one, with a period of T = 12 months. Further, a number of multiannual cycles with periods T in the ranges of 26-36, 62-85 or 113-162 months were observed, i.e. average periods of 2·5, 6·1 and 11·5 years, respectively. Indeed, most of these cycles correspond to similar cyclic parameters of HGA and further analyses are warranted to investigate such relationships. In conclusion, our study revealed the presence of multicomponent cyclic dynamics in influenza incidence by using relatively long time-series of monthly data. The specific cyclic patterns of flu incidence in Azerbaijan allows further, more specific modelling and correlations with environmental factors of similar cyclicity, e.g. HGA, to be explored. These results might contribute more widely to a better understanding of influenza dynamics and its aetiology as well as to the derivation of more precise forecasted estimates for planning and prevention purposes.
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Influenza Humana/epidemiologia , Azerbaijão/epidemiologia , Bioestatística , Humanos , IncidênciaRESUMO
Data on the dynamics of malaria incidence, admissions and mortality and their best possible description are very important to better forecast and assess the implementation of programmes to register, monitor (e.g. by remote sensing) and control the disease, especially in endemic zones. Semi-annual and seasonal cycles in malaria rates have been observed in various countries and close similarity with cycles in the natural environment (temperature, heliogeophysical activity, etc.), host immunity and/or virulence of the parasite suggested. This study aimed at confirming previous results on malaria cyclicity by exploring whether trans-year and/or multiannual cycles might exist. The exploration of underlying chronomes (time structures) was done with raw data (without smoothing) by linear and nonlinear parametric regression models, autocorrelation, spectral (Fourier) and periodogram regression analysis. The strongest cyclical patterns of detrended malaria admissions were (i) annual period of 1·0 year (12 months or seasonality); (ii) quasi-biennial cycle of about 2·25 years; and (iii) infrannual, circadecennial cycle of about 10·3 years. The seasonal maximum occurred in May with the minimum in September. Notably, these cycles corresponded to similar cyclic components of heliogeophysical activity such as sunspot seasonality and solar activity cyclicities and well-known climate/weather oscillations. Further analyses are thus warranted to investigate such similarities. In conclusion, multicomponent cyclical dynamics of cerebral malaria admissions in Papua New Guinea were observed thus allowing more specific analyses and modelling as well as correlations with environmental factors of similar cyclicity to be explored. Such further results might also contribute to and provide more precise estimates for the forecasting and prevention, as well as the better understanding, of the dynamics and aetiology of this vector-borne disease.
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Malária Cerebral/epidemiologia , Humanos , Papua Nova Guiné/epidemiologia , Periodicidade , Estudos Retrospectivos , Estações do AnoRESUMO
BACKGROUND: Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.
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Líquido da Lavagem Broncoalveolar/química , Fibrose Cística/metabolismo , Interleucina-8/análise , Pepsina A/análise , Adolescente , Biomarcadores/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Fibrose Cística/complicações , Feminino , Humanos , Lactente , Masculino , Aspiração Respiratória/diagnóstico , Aspiração Respiratória/etiologiaRESUMO
BACKGROUND: The 10q24 chromosomal region has previously been implicated in split hand foot malformation (SHFM). SHFM3 was mapped to a large interval on chromosome 10q. The corresponding dactylaplasia mouse model was linked to the syntenic locus on chromosome 19. It was shown that the two existing Dac alleles result from MusD-insertions upstream of or within Dactylin (Fbxw4). However, all efforts to find the underlying cause for the human SHFM3 have failed on the analysis of all the genes within the linkage region. Intriguingly a submicroscopic duplication within the critical locus on chromosome 10q24 was associated with the phenotype. METHODS AND RESULTS: As a part of screening for genomic rearrangements in cases with unexplained syndromic limb defects, a cohort of patients was analysed by array comparative genomic hybridisation (CGH). A 10q24 microduplication was detected in two individuals with distal limb deficiencies associated with micrognathia, hearing problems and renal hypoplasia. In addition, in a family with two affected siblings, a somatic/gonadal mosaicism for the microduplication was detected in the apparently healthy mother. Using a high resolution oligoarray further delineation of the duplication size was performed. CONCLUSIONS: The detected 10q24 genomic imbalance in our syndromic patients has a similar size to the duplication in the previously reported individuals with an isolated form of SHFM, thus extending the clinical spectrum of SHFM3. These findings clearly demonstrate the importance of array CGH in the detection of the aetiology of complex, clinically heterogeneous entities.
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Cromossomos Humanos Par 10 , Proteínas F-Box/genética , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Micrognatismo/genética , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos , Estudos de Coortes , Hibridização Genômica Comparativa , Feminino , Duplicação Gênica , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , SíndromeRESUMO
Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (pâ¯=â¯0·017) and plasma protease C1 inhibitor (pâ¯=â¯0·043), both in lower concentrations, and lipocalin-1 (pâ¯=â¯0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.
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Asma/complicações , Asma/metabolismo , Refluxo Gastroesofágico/complicações , Proteômica/métodos , Escarro/metabolismo , Adulto , Asma/epidemiologia , Asma/psicologia , Endopeptidases/metabolismo , União Europeia/organização & administração , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Humanos , Cadeias lambda de Imunoglobulina/metabolismo , Lipocalina 1/metabolismo , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Inibidores de Proteases/metabolismo , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Hospital-acquired acute kidney injury (HA-AKI) is associated with a high risk of mortality. Prediction models or rules may identify those most at risk of HA-AKI. This study externally validated one of the few clinical prediction rules (CPRs) derived in a general medicine cohort using clinical information and data from an acute hospitals electronic system on admission: the acute kidney injury prediction score (APS). DESIGN, SETTING AND PARTICIPANTS: External validation in a single UK non-specialist acute hospital (2013-2015, 12â 554 episodes); four cohorts: adult medical and general surgical populations, with and without a known preadmission baseline serum creatinine (SCr). METHODS: Performance assessed by discrimination using area under the receiver operating characteristic curves (AUCROC) and calibration. RESULTS: HA-AKI incidence within 7â days (kidney disease: improving global outcomes (KDIGO) change in SCr) was 8.1% (n=409) of medical patients with known baseline SCr, 6.6% (n=141) in those without a baseline, 4.9% (n=204) in surgical patients with baseline and 4% (n=49) in those without. Across the four cohorts AUCROC were: medical with known baseline 0.65 (95% CIs 0.62 to 0.67) and no baseline 0.71 (0.67 to 0.75), surgical with baseline 0.66 (0.62 to 0.70) and no baseline 0.68 (0.58 to 0.75). For calibration, in medicine and surgical cohorts with baseline SCr, Hosmer-Lemeshow p values were non-significant, suggesting acceptable calibration. In the medical cohort, at a cut-off of five points on the APS to predict HA-AKI, positive predictive value was 16% (13-18%) and negative predictive value 94% (93-94%). Of medical patients with HA-AKI, those with an APS ≥5 had a significantly increased risk of death (28% vs 18%, OR 1.8 (95% CI 1.1 to 2.9), p=0.015). CONCLUSIONS: On external validation the APS on admission shows moderate discrimination and acceptable calibration to predict HA-AKI and may be useful as a severity marker when HA-AKI occurs. Harnessing linked data from primary care may be one way to achieve more accurate risk prediction.
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Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Injúria Renal Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Creatinina/sangue , Feminino , Humanos , Testes de Função Renal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Reino Unido , Adulto JovemRESUMO
PURPOSE: There is wide inter-institutional variation in the interval between neoadjuvant chemoradiotherapy (NACRT) and surgery for locally advanced rectal cancer. We aimed to assess the association of magnetic resonance imaging (MRI) at 9 and 14 weeks post-NACRT; T-staging (ymrT) and post-NACRT tumour regression grading (ymrTRG) with histopathological outcomes; histopathological T-stage (ypT) and histopathological tumour regression grading (ypTRG) in order to inform decision-making about timing of surgery. PATIENTS AND METHODS: We prospectively studied 35 consecutive patients (26 males) with MRI-defined resection margin threatened rectal cancer who had completed standardized NACRT. Patients underwent a MRI at Weeks 9 and 14 post-NACRT, and surgery at Week 15. Two readers independently assessed MRIs for ymrT, ymrTRG and volume change. ymrT and ymrTRG were analysed against histopathological ypT and ypTRG as predictors by logistic regression modelling and receiver operating characteristic (ROC) curve analyses. RESULTS: Thirty-five patients were recruited. Inter-observer agreement was good for all MR variables (Kappa > 0.61). Considering ypT as an outcome variable, a stronger association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.064 vs. p = 0.010; Volume change - p = 0.062 vs. p = 0.007). Similarly, considering ypTRG as an outcome variable, a greater association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.005 vs. p = 0.042; Volume change - p = 0.004 vs. 0.055). CONCLUSION: Following NACRT, greater tumour down-staging and volume reduction was observed at Week 14. Timing of surgery, in relation to NACRT, merits further investigation. TRIAL REGISTRATION NUMBER: NCT01325909.
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Quimiorradioterapia/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Idoso , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Projetos Piloto , Estudos Prospectivos , Curva ROC , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/patologia , Reto/cirurgia , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.
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Ciclosporina/sangue , Ciclosporina/uso terapêutico , Monitoramento de Medicamentos/métodos , Rejeição de Enxerto/epidemiologia , Transplante de Rim/imunologia , Linfócitos T/imunologia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Análise de Variância , Área Sob a Curva , Biópsia , Ensaios Clínicos como Assunto , Creatinina/sangue , Feminino , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/patologia , Masculino , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Análise de Regressão , Estatísticas não Paramétricas , Linfócitos T/efeitos dos fármacos , Resultado do TratamentoRESUMO
We studied the effects of three growth factors, fibroblast growth factor (FGF4), transforming growth factor alpha (TGFalpha), and transforming growth factor beta1 (TGFbeta1), on development of diploid parthenogenetic embryos of C57BL/6 mice, which are not capable of developing to somatic stages. Parthenogenetic embryos were treated with growth factors at optimal doses in vitro at the morula--blastocyst stages and transplanted in the uterus of pseudopregnant females. FGF4 and TGFalpha improved the development of parthenogenetic embryos at the preimplantation stages and the number of blastocysts increased under the influence of TGFalpha. All three growth factors improved the implantation of embryos in the uterus. When FGF4 or TGFbeta1 were added to the nutrient medium, 2.4 or 1.6%, respectively, of parthenogenetic embryos reached the somatic stages in utero. No somitic embryos were observed in the control. The treatment of parthenogenetic embryos with two growth factors, FGF4 and TGFbeta1, simultaneously increased the amount of somatic embryos to 7.5%, while combination of three growth factors in creased the amount of such embryos to 16.7%. In the latter case, some parthenogenetic embryos reached the stage of 25-27 pairs of somites and were 2.0-2.5 mm long. The data we obtained suggest that, when combined, the growth factors FGF4, TGFalpha, and RGFbeta1 possessed a synergistic effect leading to a significant improvement of the development of parthenogenetic C57BL/6 embryos.
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Embrião de Mamíferos/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Partenogênese , Proteínas Proto-Oncogênicas/fisiologia , Fator de Crescimento Transformador alfa/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Diploide , Transferência Embrionária , Embrião de Mamíferos/citologia , Embrião de Mamíferos/efeitos dos fármacos , Desenvolvimento Embrionário , Feminino , Fator 4 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/farmacologia , Impressão Genômica , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Proteínas Proto-Oncogênicas/farmacologia , Pseudogravidez , Fator de Crescimento Transformador alfa/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1RESUMO
BACKGROUND: Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, mostly clopidogrel, is the default therapy in both acute coronary syndrome (ACS) and after intracoronary stents. It is well established that responses to antiplatelet therapy (APT), particularly clopidogrel, are subject to considerable interindividual variability. OBJECTIVES: We investigated whether responses to APT in individuals vary significantly over time. METHODS: Simultaneous assay with VerifyNow(™) and short thrombelastography (s-TEG) was performed before and at four time points over 6 months after hospital discharge in 40 patients receiving DAPT. Serum thromboxane B2 levels were also measured. RESULTS: While aspirin response units (ARU) by VerifyNow(™) and serum thromboxane B2 levels remained stable over time, arachidonic acid (AA)-mediated platelet aggregation with s-TEG (i.e. area under the curve at 15 min in AA channel, AUC15AA ) increased at 1 week compared with predischarge (P < 0.008). In addition, platelet reactivity units (PRU) by VerifyNow(™) (P = 0.046) and adenosine diphosphate (ADP)-mediated platelet aggregation with s-TEG (i.e. AUC15ADP ) also increased at 1 week compared with predischarge (P = 0.026). There were no significant changes in either platelet reactivity or rates of high on-treatment platelet reactivity while receiving clopidogrel beyond 1 week. CONCLUSIONS: This study demonstrates important variability in responses to APT within individuals between predischarge and 1 week but not thereafter. The use of a single early (predischarge) platelet function assay as an indicator of future response may therefore be flawed. The design of future strategies to assess individual responses for tailored therapy needs to take this into account.
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Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Isquemia Miocárdica/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Idoso , Área Sob a Curva , Aspirina/efeitos adversos , Biomarcadores/sangue , Plaquetas/metabolismo , Clopidogrel , Quimioterapia Combinada , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Receptores Purinérgicos P2Y12/sangue , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Reprodutibilidade dos Testes , Tromboelastografia , Tromboxano B2/sangue , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
This study assessed the effects of training and ability to execute a voluntary movement upon movement-related brain potentials (MRBPs). A self-paced thumb flexion initiated a sequence of autotriggered electrical stimuli over the median nerve that caused a twitch opposing the intended thumb extension. The MRBPs had earlier onsets during the first runs of skill acquisition than during later training sessions; they occurred earlier when they preceded a stimulus train than when they preceded a single stimulus; the onset was earlier over the vertex than over the premotor area. MRBP duration was longer during train stimulation when a voluntary effort had to be maintained against tetanic contraction. MRBP amplitude did not reflect task requirements under these experimental conditions.
Assuntos
Encéfalo/fisiologia , Atividade Motora , Movimento , Adulto , Estimulação Elétrica , Eletroencefalografia , Eletromiografia , Antebraço/inervação , Humanos , Masculino , Nervo Mediano/fisiologia , Pessoa de Meia-Idade , Músculos/inervaçãoRESUMO
Somatosensory evoked potentials (SEP) recorded from humans were elicited by a cutaneous shock to the index finger or with a ramp displacement of the finger that stretched the first dorsal interosseous muscle. A somatosensory stimulus was presented while a subject maintained a steady posture of the metacarpophalangeal joint or during a rapid voluntary abduction of the index finger. Both activities were performed against a constant opposing load of 0.15 Nm or without a load. SEPs were recorded over the postcentral arm area, together with the electromyogram of the first dorsal interosseous muscle. The major components of the SEPs were P56, N130, P174, N232 and P294. The amplitudes of all components were diminished substantially during active movement. A constant load opposing postural fixation or active movement did not influence the SEP amplitude. The amplitude of the P56 component was differentially affected by the shock or ramp stimuli. The findings demonstrate that active movement gates sensory input, while sustained tonic muscular activity with an opposing constant load does not, and that different somesthetic inputs may be processed differently during movement.
Assuntos
Potenciais Somatossensoriais Evocados , Movimento , Músculos/fisiologia , Neurônios Aferentes/fisiologia , Postura , Adulto , Estimulação Elétrica , Feminino , Dedos/inervação , Dedos/fisiologia , Humanos , Masculino , Pele/inervaçãoRESUMO
The types of chromosomal aberrations during the aging of Crepis capillaris (Hawksbeard; fam. Asteraceae) seeds were investigated. Seeds were stored at 22 degrees C for 2, 4, 6, and 8 years. Chromosomal aberrations were analyzed in metaphase chromosomes at the first and second mitotic cycles. A colchicine block was used for the differentiation of individual mitotic cycles. The frequency of chromosomal aberrations induced during seed aging gradually increased with the increase in the time of aging, reaching its maximal value after 8 years of aging. Both chromatid and chromosome types of aberrations were observed in first mitosis. At all times of aging, the frequency of chromosome-type aberrations considerably surpassed the frequency of the chromatid type. At the different times of aging, the frequency of chromosome-type aberrations was 3-4.5 times higher than that of chromatid-type aberrations. In the second mitosis, the frequency of both aberration types was low. The frequency and type of derived chromosomal aberrations observed in second mitosis corresponded to those observed in first mitosis. These results are discussed in relation to the factors inducing chromosome lesions during seed aging and the mechanism of formation of chromosomal aberrations.
Assuntos
Envelhecimento/genética , Aberrações Cromossômicas , Sementes/genética , Sementes/fisiologia , Mitose , Mutagênicos/metabolismo , Fenômenos Fisiológicos Vegetais , Plantas/genéticaRESUMO
Mechanically evoked cerebral potentials (MECP) were studied in humans standing on a movable platform with three different stance widths. A sudden platform tilt of 4 degrees produced ankle dorsiflexion and resulted in scalp potentials of five distinct components, the earliest being a positive deflection at 35/60 ms. Their latencies have shown fairly consistent values among the three stance widths, while the amplitudes underwent some significant changes under the wide stance condition as compared with tightly close feet. These findings were interpreted as purporting evidence of altered somaesthetic afferent input from lower limbs during standing with widely apart support surface.
Assuntos
Articulação do Tornozelo/fisiologia , Córtex Cerebral/fisiologia , Potenciais Evocados/fisiologia , Adulto , Eletromiografia , Humanos , Masculino , Pessoa de Meia-Idade , Postura/fisiologiaRESUMO
Species specificity concerning the two main SCE characteristics, namely frequency and localization, of "spontaneous" SCEs in plant cells (root tips of Crepis capillaris) and in human lymphocytes was investigated under comparable conditions. The FPG technique was used for detection of SCEs after bifilar incorporation of BrdU into DNA (TB-BB). Data of parallel experiments showed that the frequency of SCEs in plant cells was considerably higher than that observed in human lymphocytes--13.2 and 7.3 SCEs per cell respectively. The difference was even more pronounced when the SCE frequency was estimated on the basis of DNA content/cell (pg). Analysis of SCE distribution was limited to SCEs localized in the centromere, since contradictory results most frequently concerned this chromosome region. The data of the present experiments showed that the frequency of SCEs localized in the centromere regions of plant chromosomes was considerably lower than that observed in human chromosomes. Compared with the relative sizes of the centromere regions in the two genomes, however, these frequencies proved to be quite similar. In both systems the centromeres were involved in SCE, as could be expected for random distribution, along the length of the chromosomes.