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BACKGROUND: Investigation of the disparities in the access to experimental treatment in early-phase clinical trials is lacking. The objective of the EGALICAN-2 study was to identify the factors underpinning such inequalities. METHODS: A national prospective survey was conducted in 11 early-phase clinical trial centers (CLIP2) certified by the French National Cancer Institute. Sociodemographic, socioeconomic and medical data were collected. Univariate logistic regression models were carried out to estimate odds ratios and 90% confidence intervals associated with the effect of each study variable. A multivariate logistic regression model was built to explore the independent factors associated with the administration of the experimental treatment (C1D1). A post hoc analysis was carried out excluding female cancer patients. RESULTS: Between 2015 and 2016, 1355 patients referred from 11 CLIP2 centers in France were included in the study. Eight hundred and forty-eight patients received C1D1 (73%) and 320 patients (27%) were screening failure. Median age was 58 years (range 17-97 years) and 667 patients (54%) were female. Most patients had a metastatic disease (n = 751, 87%). In the multivariate logistic regression analysis, the significant independent factors associated with C1D1 were male sex, initial care received in a hospital with an early-phase unit and living in wealthy metropolitan areas (P values <0.05). In the post hoc analysis, the sex factor was no longer significant [odds ratio = 1.21 (95% confidence interval 0.86-1.70), P value = 0.271]. CONCLUSIONS: This study investigated the factors producing social inequalities in the context of early-phase clinical trials in oncology. Our research highlights factors of sex, care pathway and geographic location. Gynecological cancer was found to impact C1D1 significantly, unlike breast cancer. The results of this study should contribute to improve patient access to early-phase clinical trials.
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Neoplasias da Mama , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , França/epidemiologia , Neoplasias da Mama/diagnósticoRESUMO
BACKGROUND: The knowledge base on physical activity and sedentary behaviour in adults with Down syndrome (DS) may advance by accelerometer calibration studies. This study aimed to develop cut-points for sedentary behaviour and moderate-to-vigorous physical activity (MVPA) for adults with DS based on output from accelerometers worn on the dominant and non-dominant hips. METHODS: Sixteen adults with DS (10 men; age 31 ± 15 years) performed 12 tasks including sedentary behaviours and physical activities. We obtained metabolic equivalents (METs) with indirect calorimetry and vector magnitude (VM) output from triaxial accelerometers (wGT3X-BT, ActiGraph) worn on the dominant and non-dominant hips. Receiver operating characteristic curves were used to identify optimal VM cut-points that maximised sensitivity and specificity. RESULTS: Overall classification accuracy was very high (area under the ROC curve: 0.95 and 0.92 for sedentary and MVPA models, respectively). For the non-dominant hip, the optimal VM cut-points were (1) sedentary behaviour ≤236 counts·min-1 and (2) MVPA ≥2167 counts·min-1 . For the dominant hip, optimal cut-points were (1) sedentary behaviour ≤243 counts·min-1 and (2) MVPA ≥2092 counts·min-1 . CONCLUSIONS: The presented VM cut-points for sedentary behaviour and MVPA for adults with DS had high classification accuracy. There were small differences in accelerometer cut-points between the dominant and non-dominant hip.
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Síndrome de Down , Comportamento Sedentário , Masculino , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Calibragem , Exercício Físico , AcelerometriaRESUMO
Spatial arrangement of distinct Amazonian environments through time and its effect on specialized biota remain poorly known, fueling long-lasting debates about drivers of biotic diversification. We address the late Quaternary sediment deposition that assembled the world's largest seasonally flooded ecosystems. Genome sequencing was used to reconstruct the demographic history of bird species specialized in either early successional vegetation or mature floodplain forests. Sediment deposition that built seasonally flooded habitats accelerated throughout the Holocene (last 11,700 years) under sea level highstand and intensification of the South American Monsoon, at the same time as global increases in atmospheric methane concentration. Bird populations adapted to seasonally flooded habitats expanded due to enlargement of Amazonian river floodplains and archipelagos. Our findings suggest that the diversification of the biota specialized in seasonally flooded habitats is coupled to sedimentary budget changes of large rivers, which rely on combined effects of sea level and rainfall variations.
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Ecossistema , Inundações , Animais , Aves , Florestas , RiosRESUMO
BACKGROUND: Access to clinical trials and especially early-phase trials (ECT) is an important issue in geriatric oncology. As cancer can be considered an age-related disease because the incidence of most cancers increases with age, new drugs should also be evaluated in older patients to assess their safety and efficacy. The EGALICAN-2 study was primarily designed to identify social and/or regional inequalities regarding access to ECT. We focused on the factors of inequalities in access to ECT in older patients. PATIENTS AND METHODS: During a 1-year period (2015-2016), a survey was conducted in 11 early-phase units certified by the French National Cancer Institute. RESULTS: A total of 1319 patients were included in the analyses: 1086 patients (82.3%) were <70 years and 233 patients (17.7%) were >70 years. The most common tumor types at referral in older patients were gastrointestinal (19.3%), hematological (19.3%), and thoracic tumors (18.0%). Most patients referred to the phase I unit had signed informed consent and the rate was similar across age (92.7% in younger patients versus 90.6% in older patients; P = 0.266). The rate of screening failure was also similar across age (28.5% in younger patients versus 24.3% in older patients; P = 0.219). Finally, in older patients, univariate analyses showed that initial care received in the hospital having a phase I unit was statistically associated with first study drug administration (odds ratio 0.49, 90% confidence interval 0.27-0.88; P = 0.045). CONCLUSIONS: Older patients are underrepresented in early clinical trials with 17.7% of patients aged ≥70 years compared with the number of new cases of cancer in France (50%). However, when invited to participate, older patients were prone to sign informed consent.
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Neoplasias , Idoso , Ensaios Clínicos como Assunto , França/epidemiologia , Humanos , Incidência , Neoplasias/tratamento farmacológico , Neoplasias/terapiaRESUMO
BACKGROUND: Triaxial accelerometer output [vector magnitude (VM) counts] may better estimate physical activity intensity as reflected in the rate of oxygen uptake (VÌO2 ) than the traditional vertical axis (VA) counts in adults with Down syndrome (DS). This study examined the accuracy of VM vs. VA counts in estimating VÌO2 in adults with and without DS across different physical activities and sedentary behaviours. METHODS: Sixteen adults with DS (10 men and 6 women; 31 ± 15 years) and 19 adults without DS (10 men and 9 women; 24 ± 5 years) performed 12 tasks. VÌO2 was measured by portable spirometer (K4b2 , Cosmed) and VM and VA with an accelerometer (wGT3X-BT, Actigraph). RESULTS: Vector magnitude and VA were significant predictors of VÌO2 in adults with DS (P < 0.001; R2 = 0.74 and 0.65, respectively) and adults without DS (P < 0.001; P < 0.001; R2 = 0.75 and 0.61, respectively). Absolute error of prediction was significantly smaller for VM than VA for sitting, playing app, drawing, sweeping, standing and basketball (P ≤ 0.005), but smaller for VA than VM for walking at 0.8 m·s-1 (P = 0.005). Bland-Altman plots for adults with and without DS indicated narrower limits of agreement for VM than VA (-5.57 to 5.57 and -6.44 to 6.44 mL·kg-1 ·min-1 ; -6.21 to 6.17 and -7.75 to 7.74 mL·kg-1 ·min-1 , respectively). CONCLUSIONS: Vector magnitude and VA are significant predictors of VÌO2 in adults with and without DS, yet VM more accurately estimated VÌO2 than VA for most tasks. Development of accelerometer-based prediction of physical activity levels in adults with and without DS may improve by utilising VM counts.
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Síndrome de Down , Acelerometria , Adulto , Exercício Físico , Feminino , Humanos , Masculino , Oxigênio , CaminhadaRESUMO
OBJECTIVES: Both the political appetite for a science-based coronavirus disease 2019 (COVID-19) policy and its acceptability to the public are little understood, at a time of sharp distrust not only of governments but also of scientists and their journals' review practices. We studied the case of France, where the independent Scientific Council on COVID-19 was appointed by President Macron on March 12, 2020. STUDY DESIGN: We conducted a survey on a representative sample of the French adult population. METHODS: Our data were collected by the French Institute of Public Opinion using a self-administered online questionnaire. This was completed by a sample of 1016 people stratified to match French official census statistics for gender, age, occupation, and so on. We conducted statistical analysis using Python (Pandas-SciPy-Statsmodels) with Chi-squared and Wilcoxon rank-sum tests to control for statistical significance. RESULTS: Intense media coverage has given the council a very high public profile, with three respondents out of four (73%) having heard about it. Perceptions are positive but complex. French citizens expect science to be important in political decision-making. Four of five (81.5%) want political decisions, in general, to be based on scientific knowledge. But one in two (55%) says that the government has not relied enough on science and only 36% are satisfied with the government's crisis management to date. Although most feel that the council has a legitimate advisory role even in situations of uncertainty (only 15% disagree), it is not perceived as fully independent. Only 44% think that it directly represents the scientific community, and only one of three people considers it completely independent from the government (39%) and the pharmaceutical industry (36%). CONCLUSIONS: Our study confirms that while the transparency of scientific advice is important, it alone cannot ensure public confidence in political decision-making. We suggest that efforts made today to instill a 'science-savvy' public culture-one that allows the complex articulation between scientific knowledge, uncertainty, and political decision-making to be understood and accounted for would greatly benefit evidence-based policy in future crises.
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COVID-19/prevenção & controle , Opinião Pública , Política Pública , Ciência , Adulto , COVID-19/epidemiologia , Meios de Comunicação , Feminino , França/epidemiologia , Governo , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
The purpose of this study was to assess the influence of resection quality on overall survival and disease-free survival in children with atypical teratoid-rhabdoid tumors (ATRT). The study included children younger than 18 years old for the period from 2008 to 2019. There were 134 interventions in 105 patients with ATRT including 11 redo resections («second-look¼ surgery) and 18 procedures for tumor recurrence. Age of patients ranged from 2 to 168 months (median 21 months). Patients with supratentorial tumors prevailed (50.5%), infratentorial neoplasms were diagnosed in 45.7% of patients, spinal cord lesion - 3.8% of cases. At the first stage, all patients underwent surgical treatment. Total resection was achieved in 34 (32.4%) patients, subtotal - 37 (35.2%) patients, partial resection - 30 (28.6%) patients. Biopsy was performed in 4 (3.8%) patients. Quality of resection and age at surgery significantly influenced overall and disease-free survival. Extended resection of tumor followed by adjuvant chemo- and radiotherapy are required to improve survival although ATRTs are high-grade neoplasms with poor prognosis.
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Neoplasias do Sistema Nervoso Central , Neoplasias Infratentoriais , Tumor Rabdoide , Teratoma , Adolescente , Neoplasias do Sistema Nervoso Central/cirurgia , Criança , Intervalo Livre de Doença , Humanos , Lactente , Tumor Rabdoide/cirurgia , Teratoma/cirurgiaRESUMO
The potential of microalgae Spirulina platensis to the production of nitrogenous compounds in liquid fraction via slow pyrolysis was evaluated. Aiming to identify the best condition which maximized liquid yield, the effects of operational conditions mass load, temperature, and heating rate were evaluated using Experimental Design and Response Surface Methodology techniques and optimized with Differential Evolution methodology. The composition of liquid fraction was analyzed by GC-MS and the effect of the same operational conditions in nitrogenous compounds formation was analyzed. The separation of nitrogenous compounds was evaluated by extraction and adsorption techniques. The results indicated that the heating rate significantly impacted both the liquid yield and the formation of the nitrogenous compounds. At optimal conditions, a maximum liquid yield of 64.59% was obtained. The extraction and adsorption processes showed to be promising routes for the purification of nitrogenous compounds, however, extraction was more selective to separate them.
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Microalgas , Spirulina , Biocombustíveis , Compostos de Nitrogênio , PiróliseRESUMO
Caprine arthritis encephalitis (CAE) is a chronic disease caused by a retrovirus from the Lentivirus genus. No effective vaccines or treatments exist, and therefore genetic selection for CAE resistance might be a feasible alternative. To our best knowledge, no other studies have investigated the genetic architecture of CAE resistance in dairy goats. In this context, this study was designed to estimate genetic parameters for CAE infection in Alpine and Saanen goats using a Bayesian threshold model. A total of 542 adult goats (and >3-generation pedigree), which were group-housed in a population with high CAE prevalence, were tested based on a serological infection assessment test (negative = 1 or positive = 2) and used for this study. Genetic parameters were estimated using the BLUPF90 family programs. There was considerable genetic variability for CAE resistance, and pedigree-based heritability was significantly different from zero (0.026 < heritability < 0.128). Our findings indicate that the prevalence of CAE in goat herds can be reduced or eliminated through direct genetic selection for CAE resistance in addition to proper management strategies.
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Vírus da Artrite-Encefalite Caprina , Predisposição Genética para Doença , Doenças das Cabras/virologia , Infecções por Lentivirus/veterinária , Animais , Teorema de Bayes , Doenças das Cabras/epidemiologia , Cabras , Infecções por Lentivirus/genética , Infecções por Lentivirus/virologiaRESUMO
INTRODUCTION: Glioneuronal tumors (GNT) are usually found in children (less than 1.5% of all neoplasms of the brain). With rare exceptions, they are benign and usually manifest only by epilepsy, which is quite often resistant to treatment with AE drugs. Tumor removal usually helps to cope with epileptic seizures, however, a number of issues regarding diagnosis and surgical treatment (interpretation of morphological data and classification, epileptogenesis and topography of the epileptogenic zone, the value of intraoperative invasive EEG and the optimal volume of resection) remain debatable. AIM: To describe the morphology, electro-clinical picture and MR-semiology in patients with gloneuronal brain tumors, as well as to analyse the results of their surgical treatment and the factors determining its outcome. MATERIAL AND METHODS: 152 children with a median age of 8 years were treated surgically (There were 64 gangliogliomas, 73 DNT, 15 cases where the tumor classification failed - GNT NOS). In children under 2 years of age, temporal localization of the tumor prevailed. In 81 cases, ECoG was used during the operation. Surgical treatment complications: transient neurological deficit (in 15 cases); hematomas removed without consequences (in 2 cases), infectious (osteomyelitis of bone bone flap in 2 cases). We analyzed: the age of the epilepsy onset (median - 4 years 7 months) and its duration (median - 23.5 months), the type of seizures, as well as the features of MR-semiology and morphology of tumors and adjacent areas of the brain. The volume of tumor resection was verified by MRI (in 101 cases) and CT (in each case). The follow-up was collected through face-to-face meetings, with repeated video EEG and MRI, as well as telephone interviews. We studied the effect of a number of parameters characterizing the patient and features of his/her operation on the outcome of treatmen. RESULTS: Among 102 patients in whom the follow-up history is one year or more (median - 2 years), a favorable outcome (Engel IA) was observed in 86 of them (84%); 55 of them (54%) at the time of the last examination stopped drug AE treatment. Radical tumor removal and younger age at the time of surgery were statistically significantly associated with a favorable result. CONCLUSION: In children with gloneuronal brain tumors, removal of the tumor is effective and relatively safe in the treatment of symptomatic epilepsy. Radical tumor resection and earlier intervention are the most important prerequisites for a favorable outcome and persistent remission of seizures.
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Neoplasias Encefálicas/cirurgia , Epilepsia/cirurgia , Criança , Eletroencefalografia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: H1 receptor antagonists are commonly used for the treatment of allergic diseases. The aim of this study was to find out, if antihistaminic compounds like mepyramine have the ability to influence the activity of antibacterials. Therefore, the checkerboard method was chosen to detect these possible effects in vitro. Studies were performed with two different Escherichia coli (E. coli) strains as test microbes, treated with antibacterials in combination with mepyramine. RESULTS: The minimum inhibitory concentration (MIC) of E. coli ATCC® 25922™ and E. coli PIG 01 was reduced by combinations of the tested antibacterials with mepyramine. CONCLUSIONS: These results have to be confirmed in vivo, before the use of antihistamines should be considered as potential way to minimize the amount of used antibacterials for treatment of E. coli infections.
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Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antibacterianos/administração & dosagem , Sinergismo Farmacológico , Quimioterapia Combinada , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Pirilamina/administração & dosagem , Pirilamina/farmacologiaRESUMO
BACKGROUND: Basal cell carcinomas are the most common periocular malignant tumor. In advanced periocular basal cell carcinoma, vismodegib is a new treatment option which might potentially avoid surgical eye removal. CASE REPORT: We treated a 76-year-old patient unwilling to consent to surgery with vismodegib for advanced periocular basal cell carcinoma on the left forehead that had already undergone several previous treatments. After initial partial remission, the tumor regrew under ongoing therapy, so that radical surgical excision including orbital exenteration was performed. Unfortunately, the patient died thereafter due to septic multi-organ failure. CONCLUSION: Basal cell carcinoma and its new treatment options are gaining importance for ophthalmology due to rising incidence and prevalence rates. Vismodegib is a new encouraging option. However, for advanced tumors, it must be resolved whether complete histological remission may be achieved to avoid surgical intervention, or whether the area of resection can be significantly reduced. Current multicenter studies investigate these aspects further (ClinicalTrails.gov identifier: NCT03035188).
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Carcinoma Basocelular , Neoplasias Cutâneas , Idoso , Enucleação Ocular , Humanos , IncidênciaRESUMO
AIM: To investigate changes in cerebral perfusion in patients with unilateral internal carotid artery occlusion before and after surgical revascularization of the brain, depending on the clinical efficacy of surgical treatment. MATERIAL AND METHODS: The study included 60 patients with unilateral ICA occlusions who underwent placement of an extra-intracranial microvascular anastomosis (EICMA). All patients underwent a CT perfusion study before and after cerebral revascularization. In addition, the degree of neurological deficit was evaluated before surgery and during follow-up (3 and 8-10 months) using the NIHSS score. RESULTS: All patients were divided into 3 groups, depending on the results of surgical treatment: objective improvement (43 patients), no changes (14 patients), and worsening of clinical symptoms (3 patients). In each group, the absolute and relative perfusion parameters (MTT, CBV, and CBF) were analyzed to identify the perfusion criteria for the EICMA efficacy. A significant relationship between the clinical efficacy of EICMA and a baseline perfusion deficit and its change after anastomosis placement was found. CONCLUSION: Placement of EICMA is effective treatment for patients with symptomatic ICA occlusions and an increase in the blood transit time in the hemisphere ipsilateral to occlusion by more than 40% compared to that in the opposite side provided that perfusion is recovered in more than one area of the MCA territory (in accordance with the ASPECTS scale).
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Artéria Carótida Interna , Estenose das Carótidas , Angiografia por Ressonância Magnética , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Anastomose Cirúrgica/métodos , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. PATIENTS AND METHODS: Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic. The RecPRAME dose was 20, 100 or 500 µg in cohorts 1, 2 and 3, respectively, with a fixed dose of AS15. Adverse events (AEs), including predefined dose-limiting toxicity (DLT) and the anti-PRAME humoral response (ELISA), were coprimary end points. Cellular immune responses were evaluated using in vitro assays. RESULTS: 66 patients were treated (20, 24 and 22 in the respective cohorts). AEs considered by the investigator to be causally related were mostly grade 1 or 2 injection site symptoms, fatigue, chills, fever and headache. Two DLTs (grade 3 brain oedema and proteinuria) were recorded in two patients in two cohorts (cohorts 2 and 3). All patients had detectable anti-PRAME antibodies after four immunisations. Percentages of patients with predefined PRAME-specific-CD4+T-cell responses after four immunisations were similar in each cohort. No CD8+ T-cell responses were detected. CONCLUSIONS: The PRAME immunotherapeutic had an acceptable safety profile and induced similar anti-PRAME-specific humoral and cellular immune responses in all cohorts. As per protocol, the phase II study segment was initiated to further evaluate the 500â µg PRAME immunotherapeutic dose. TRIAL REGISTRATION NUMBER: NCT01149343, Results.
RESUMO
Cutaneous dipththeria is an infectious bacterial disease endemic in tropical regions, but rarely diagnosed in Germany. Following travel in Sri Lanka, a 60-year-old German presented to our dermatological clinic with a skin ulcer and extensive erythematous erosive edema of his left foot. Corynebacterium diphtheriae was isolated from a swab of the lesion. There were no clinical signs of toxic diphtheria. The patient was treated with penicillin G and erythromycin, followed by a slow healing of the lesion. The isolated strain could be identified as toxigenic C. diphtheriae mitis. Due to increased travel activity, dermatologists should have uncommon infections like cutaneous diphtheria in mind.
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Difteria/diagnóstico , Difteria/tratamento farmacológico , Úlcera do Pé/diagnóstico , Úlcera do Pé/tratamento farmacológico , Lacerações/tratamento farmacológico , Viagem , Antibacterianos/uso terapêutico , Corynebacterium diphtheriae/isolamento & purificação , Difteria/microbiologia , Quimioterapia Combinada , Eritromicina/administração & dosagem , Úlcera do Pé/microbiologia , Alemanha , Humanos , Lacerações/diagnóstico , Lacerações/microbiologia , Pessoa de Meia-Idade , Penicilina G/administração & dosagem , Sri Lanka , Resultado do TratamentoRESUMO
BACKGROUND: Asthma is a disease affecting many locations throughout the airway. Most studies have used spirometry as the primary assessment of airway obstruction, a method that may be less sensitive in regard to peripheral airway obstruction. The aim of this study was to elucidate the associations between asthma phenotypes based on age of onset and duration of symptoms, and (i) spirometry and (ii) small airway involvement measured by impulse oscillometry (IOS) in adolescence. METHODS: Children and adolescents taking part in BAMSE, a prospective birth cohort study, performed spirometry at 8 and 16 years and IOS at 16 years of age. Based on data collected in questionnaires, children were categorized into the following groups: 'never asthma', 'early transient asthma', 'early persistent asthma', and 'late onset asthma'. RESULTS: Compared with the never asthma group, all asthma groups were associated with lower FEV1 at 16 years of age (early transient-119 ml, 95% confidence interval -204 to -34; early persistent-410 ml, 95%CI -533; -287; and late onset-148 ml, 95%CI -237; -58). Between 8 and 16 years, significantly less increase in FEV1 was observed in the early persistent and late onset groups. The small airway index 'R5-20 ' was significantly associated with active asthma at 16 years, but not transient asthma. CONCLUSIONS: All asthma phenotypes studied were negatively associated with FEV1 in adolescence. IOS measurements indicated that active asthma could be associated with small airway impairments. These results provide new insights into the physiology underlying wheezing phenotypes based on age of onset and duration of disease.
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Asma/fisiopatologia , Pulmão/fisiopatologia , Sons Respiratórios/fisiopatologia , Adolescente , Idade de Início , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Criança , Estudos de Coortes , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Hipersensibilidade/epidemiologia , Masculino , Oscilometria , Fenótipo , Estudos Prospectivos , Testes de Função Respiratória , Espirometria , Inquéritos e Questionários , Suécia/epidemiologiaRESUMO
We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation.
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Aconitum/química , Analgésicos/farmacologia , Dor/prevenção & controle , Convulsões/prevenção & controle , Ácido Acético , Aconitina/análogos & derivados , Aconitina/isolamento & purificação , Aconitina/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Analgésicos/isolamento & purificação , Animais , Animais não Endogâmicos , Artrite Experimental/induzido quimicamente , Artrite Experimental/fisiopatologia , Dipirona/farmacologia , Adjuvante de Freund , Injeções Intraperitoneais , Camundongos , Dor/induzido quimicamente , Dor/fisiopatologia , Extratos Vegetais/química , Ratos , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Vocalização Animal/efeitos dos fármacosRESUMO
The alewife (Alosa pseudoharengus) is a clupeid that undergoes larval and juvenile development in freshwater preceding marine habitation. The purpose of this study was to investigate osmoregulatory mechanisms in alewives that permit homeostasis in different salinities. To this end, we measured physiological, branchial biochemical and cellular responses in juvenile alewives acclimated to freshwater (0.5 p.p.t.) or seawater (35.0 p.p.t.). Plasma chloride concentration was higher in seawater-acclimated than freshwater-acclimated individuals (141 mmol l(-1) vs 134 mmol l(-1)), but the hematocrit remained unchanged. In seawater-acclimated individuals, branchial Na(+)/K(+)-ATPase (NKA) activity was higher by 75%. Western blot analysis indicated that the abundance of the NKA α-subunit and a Na(+)/K(+)/2Cl(-) cotransporter (NKCC1) were greater in seawater-acclimated individuals by 40% and 200%, respectively. NKA and NKCC1 were localized on the basolateral surface and tubular network of ionocytes in both acclimation groups. Immunohistochemical labeling for the cystic fibrosis transmembrane conductance regulator (CFTR) was restricted to the apical crypt of ionocytes in seawater-acclimated individuals, whereas sodium/hydrogen exchanger 3 (NHE3) labeling was present on the apical surface of ionocytes in both acclimation groups. Ionocytes were concentrated on the trailing edge of the gill filament, evenly distributed along the proximal 75% of the filamental axis and reduced distally. Ionocyte size and number on the gill filament were not affected by salinity; however, the number of lamellar ionocytes was significantly lower in seawater-acclimated fish. Confocal z-series reconstructions revealed that mature ionocytes in seawater-acclimated alewives occurred in multicellular complexes. These complexes might reduce paracellular Na(+) resistance, hence facilitating Na(+) extrusion in hypo-osmoregulating juvenile alewives after seaward migration.
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Transporte de Íons/fisiologia , Trocadores de Sódio-Hidrogênio/metabolismo , Simportadores de Cloreto de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Cloretos/sangue , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Peixes , Água Doce , Brânquias/citologia , Brânquias/metabolismo , Brânquias/fisiologia , Salinidade , Água do Mar , Trocador 3 de Sódio-Hidrogênio , Membro 2 da Família 12 de Carreador de SolutoRESUMO
We report three historical cases of severe vitamin A intoxication in anglers who had consumed reef fish liver caught in Bermuda. The subsequent analyses of 35 fish livers from seven different fish species revealed that very high concentrations of vitamin A exist in tropical fish liver, even in noncarnivorous fish species. Large variations in concentrations were observed between specimens and between species. The angling population and (especially) pregnant women should be advised of this potential health threat.
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Peixes/metabolismo , Contaminação de Alimentos/análise , Hipervitaminose A/etiologia , Fígado/metabolismo , Animais , Bermudas , Humanos , Hipervitaminose A/complicações , Hipervitaminose A/imunologia , Medição de Risco , Alimentos Marinhos/análise , Especificidade da EspécieRESUMO
OBJECTIVE: The purpose of this study was to compare Tanita tetrapolar foot-to-foot bioelectrical impedance analysis (Model TBF-310, Tanita Corporation of America, Inc, Arlington Heights, IL; Tanita-BIA) and fan beam dual-energy X-ray absorptiometry (Hologic Discovery A v12.6, Waltham, MA; DXA) in diabetic patients. METHODS: Seventy Hispanic diabetic participants (23 male, 47 female; mean age: 53.03 ± 10.32 yrs; mean weight: 81.45 ± 17.65 kg; and mean body mass index: 31.40 ± 6.80 kg/m(2)) were selected from the Loma Linda University En Balance culturally-sensitive Spanish diabetes education program using the baseline data. RESULTS: DXA vs Tanita-BIA fat mass (FM), percent fat mass (%FM), and fat-free mass (FFM) were compared using Pearson's (FM: 0.96, %FM: 0.91, and FFM: 0.95), and Spearman's rank (FM: 0.94, %FM: 0.91, and FFM: 0.93) correlation coefficients. Bland-Altman analyses were also used to compare the difference (DXA - BIA) vs average of DXA and BIA results and showed general agreement between the two methods. When Tanita-BIA was regressed onto DXA, the adjusted R(2) was: FM=0.91; %FM=0.83; FFM=0.90. Gender combined concordance correlations with 95% confidence intervals were calculated using a bootstrap re-sampling of the data and found high associations [FM: 0.93 (95% CI: 0.89, 0.96)], [%FM: 0.86 (95% CI: 0.79, 0.90)], and [FFM: 0.93 (95% CI: 0.89, 0.96)]. CONCLUSION: Tanita-BIA may provide valid measures of fat, percent body fat and fat-free mass in Hispanic diabetics, and could be a convenient and practical approach for assessment in community-based research.