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BACKGROUND: Little is known about vaccine effectiveness over time among adolescents, especially against the SARS-CoV-2 omicron (B.1.1.529) variant. This study assessed the associations between time since two-dose vaccination with BNT162b2 and the occurrence of symptomatic SARS-CoV-2 infection and severe COVID-19 among adolescents in Brazil and Scotland. METHODS: We did test-negative, case-control studies in adolescents aged 12-17 years with COVID-19-related symptoms in Brazil and Scotland. We linked records of SARS-CoV-2 RT-PCR and antigen tests to national vaccination and clinical records. We excluded tests from individuals who did not have symptoms, were vaccinated before the start of the national vaccination programme, received vaccines other than BNT162b2 or a SARS-CoV-2 booster dose of any kind, or had an interval between their first and second dose of fewer than 21 days. Additionally, we excluded negative SARS-CoV-2 tests recorded within 14 days of a previous negative test, negative tests recorded within 7 days after a positive test, any test done within 90 days after a positive test, and tests with missing sex and location information. Cases (SARS-CoV-2 test-positive adolescents) and controls (test-negative adolescents) were drawn from a sample of individuals in whom tests were collected within 10 days of symptom onset. We estimated the adjusted odds ratio and vaccine effectiveness against symptomatic COVID-19 for both countries and against severe COVID-19 (hospitalisation or death) for Brazil across fortnightly periods. FINDINGS: We analysed 503 776 tests from 2 948 538 adolescents in Brazil between Sept 2, 2021, and April 19, 2022, and 127 168 tests from 404 673 adolescents in Scotland between Aug 6, 2021, and April 19, 2022. Vaccine effectiveness peaked at 14-27 days after the second dose in both countries during both waves, and was significantly lower against symptomatic infection during the omicron-dominant period in Brazil (64·7% [95% CI 63·0-66·3]) and in Scotland (82·6% [80·6-84·5]), than it was in the delta-dominant period (80·7% [95% CI 77·8-83·3] in Brazil and 92·8% [85·7-96·4] in Scotland). Vaccine efficacy started to decline from 27 days after the second dose for both countries, reducing to 5·9% (95% CI 2·2-9·4) in Brazil and 50·6% (42·7-57·4) in Scotland at 98 days or more during the omicron-dominant period. In Brazil, protection against severe disease remained above 80% from 28 days after the second dose and was 82·7% (95% CI 68·8-90·4) at 98 days or more after receiving the second dose. INTERPRETATION: We found waning vaccine protection of BNT162b2 against symptomatic COVID-19 infection among adolescents in Brazil and Scotland from 27 days after the second dose. However, protection against severe COVID-19 outcomes remained high at 98 days or more after the second dose in the omicron-dominant period. Booster doses for adolescents need to be considered. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Health Data Research UK BREATHE Hub, Fiocruz, Fazer o Bem Faz Bem programme, Brazilian National Research Council, and Wellcome Trust. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
Assuntos
COVID-19 , Humanos , Adolescente , COVID-19/epidemiologia , COVID-19/prevenção & controle , Brasil/epidemiologia , Estudos de Casos e Controles , Vacina BNT162 , Eficácia de Vacinas , SARS-CoV-2RESUMO
BACKGROUND: Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon). METHODS: In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs. FINDINGS: 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks. INTERPRETATION: We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19. FUNDING: UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.
Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/mortalidade , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/administração & dosagem , Eficácia de Vacinas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Hospitalização , Humanos , Imunização Secundária , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/imunologia , Escócia/epidemiologia , Fatores de Tempo , VacinaçãoRESUMO
The landscape of cancer treatment has improved over the past decades, aiming to reduce systemic toxicity and enhance compatibility with the quality of life of the patient. However, at the therapeutic level, metastatic cancer remains hugely challenging, based on the almost inevitable emergence of therapy resistance. A small subpopulation of cells able to survive drug treatment termed the minimal residual disease may either harbor resistance-associated mutations or be phenotypically resistant, allowing them to regrow and become the dominant population in the therapy-resistant tumor. Characterization of the profile of minimal residual disease represents the key to the identification of resistance drivers that underpin cancer evolution. Therapeutic regimens must, therefore, be dynamic and tailored to take into account the emergence of resistance as tumors evolve within a complex microenvironment in vivo. This requires the adoption of new technologies based on the culture of cancer cells in ways that more accurately reflect the intratumor microenvironment, and their analysis using omics and system-based technologies to enable a new era in the diagnostics, classification, and treatment of many cancer types by applying the concept "from the cell plate to the patient." In this chapter, we will present and discuss 3D model building and use, and provide comprehensive information on new genomic techniques that are increasing our understanding of drug action and the emergence of resistance.
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Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Desenvolvimento de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Qualidade de Vida , Biologia de Sistemas , Microambiente TumoralRESUMO
Specialized interactions between insects and the plants that they consume are one of the most ubiquitous and consequential ecological associations on the plant. Decades of investigation suggest that a narrow diet favors an individual phytophagous insect's performance relative to a dietary generalist. However, this body of research has tended to approach questions of diet breadth and host usage from the perspective of temperate plant-insect associations. Relationships between diet breadth, host usage, and variation in tropical insect preference and performance remain largely uninvestigated. Here we characterize how variation in diet breadth and host usage affect oviposition preference, development, survival, and gain in mass of a Neotropical tortoise beetle Chelymorpha alternans Boheman 1854 (Coleoptera: Chrysomelidae), using a split-brood, sibling experimental design. Host performance was measured after splitting broods among four no-choice host diets. Groups consuming single hosts varied among themselves in developmental time and survival from larva to adult. Performance did not vary among groups consuming multiple and single hosts. Oviposition preference was measured in choice and no-choice tests. Females displayed preference for the original host in both experiments. Developmental time and survival of offspring sourced from the no-choice experiment was measured for two complete generations to explore correlations with female oviposition preference. Preference for the original host correlated with high survivorship and an intermediate developmental time. Survivorship and time to develop were also high on an alternative host that was less preferred. Departures from predictions of prevailing preference-performance hypotheses suggest that host usage presents C. alternans with fitness trade-offs.
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Besouros/crescimento & desenvolvimento , Dieta , Herbivoria , Ipomoea batatas , Oviposição , Animais , Feminino , Larva/crescimento & desenvolvimento , Masculino , PanamáRESUMO
Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathways linked to their proliferation and invasiveness. In particular, ω-3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study, 16-(4'-chloro-3'-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω-3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI < 0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.
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ABSTRACTDual sequential external defibrillation (DSED) is the process of near simultaneous discharge of two defibrillators with differing pad placement to terminate refractory arrhythmias. Previously used in the electrophysiology suite, this technique has recently been used in the emergency department and prehospital setting for out-of-hospital cardiac arrest (OHCA). We present a case of successful DSED in the emergency department with neurologically intact survival to hospital discharge after refractory ventricular fibrillation (RVF) and review the putative mechanisms of action of this technique.
Assuntos
Desfibriladores , Serviço Hospitalar de Emergência/organização & administração , Parada Cardíaca Extra-Hospitalar/terapia , Fibrilação Ventricular/terapia , Eletrocardiografia , Serviços Médicos de Emergência , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Five ascosporogenous yeast strains related to the genus Kazachstania were isolated. Two strains (CLIB 1764T and CLIB 1780) were isolated from French sourdoughs; three others (UFMG-CM-Y273T, UFMG-CM-Y451 and UFMG-CM-Y452) were from rotting wood in Brazil. The sequences of the French and Brazilian strains differed by one and three substitutions, respectively, in the D1/D2 large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS). The D1/D2 LSU rRNA sequence of these strains differed by 0.5 and 0.7 % from Kazachstania exigua, but their ITS sequences diverged by 8.1 and 8.3 %, respectively, from that of the closest described species Kazachstania barnettii. Analysis of protein coding sequences of RPB1, RPB2 and EF-1α distinguished the French from the Brazilian strains, with respectively 3.3, 6 and 11.7 % substitutions. Two novel species are described to accommodate these newly isolated strains: Kazachstania saulgeensis sp. nov. (type strain CLIB 1764T=CBS 14374T) and Kazachstania serrabonitensis sp. nov. (type strain UFMG-CM-Y273T=CLIB 1783T=CBS 14236T). Further analysis of culture collections revealed a strain previously assigned to the K. exigua species, but having 3.8 % difference (22 substitutions and 2 indels) in its ITS with respect to K. exigua. Hence, we describe a new taxon, Kazachstania australis sp. nov. (type strain CLIB 162T=CBS 2141T), to accommodate this strain. Finally, Candida humilis and Candida pseudohumilis are reassigned to the genus Kazachstania as new combinations. On the basis of sequence analysis, we also propose that Candida milleri and Kazachstania humilis comb. nov. are conspecific.
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Filogenia , Saccharomycetales/classificação , Brasil , Pão/microbiologia , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , França , Genes Fúngicos , Técnicas de Tipagem Micológica , Fator 1 de Elongação de Peptídeos/genética , RNA Polimerase II/genética , RNA Ribossômico/genética , Saccharomycetales/genética , Saccharomycetales/isolamento & purificação , Análise de Sequência de DNA , Madeira/microbiologiaRESUMO
Tropical peatlands play an important role in the global storage and cycling of carbon (C) but information on carbon dioxide (CO2) and methane (CH4) fluxes from these systems is sparse, particularly in the Neotropics. We quantified short and long-term temporal and small scale spatial variation in CO2 and CH4 fluxes from three contrasting vegetation communities in a domed ombrotrophic peatland in Panama. There was significant variation in CO2 fluxes among vegetation communities in the order Campnosperma panamensis > Raphia taedigera > Cyperus. There was no consistent variation among sites and no discernible seasonal pattern of CH4 flux despite the considerable range of values recorded (e.g. -1.0 to 12.6 mg m(-2) h(-1) in 2007). CO2 fluxes varied seasonally in 2007, being greatest in drier periods (300-400 mg m(-2) h(-1)) and lowest during the wet period (60-132 mg m(-2) h(-1)) while very high emissions were found during the 2009 wet period, suggesting that peak CO2 fluxes may occur following both low and high rainfall. In contrast, only weak relationships between CH4 flux and rainfall (positive at the C. panamensis site) and solar radiation (negative at the C. panamensis and Cyperus sites) was found. CO2 fluxes showed a diurnal pattern across sites and at the Cyperus sp. site CO2 and CH4 fluxes were positively correlated. The amount of dissolved carbon and nutrients were strong predictors of small scale within-site variability in gas release but the effect was site-specific. We conclude that (i) temporal variability in CO2 was greater than variation among vegetation communities; (ii) rainfall may be a good predictor of CO2 emissions from tropical peatlands but temporal variation in CH4 does not follow seasonal rainfall patterns; and (iii) diurnal variation in CO2 fluxes across different vegetation communities can be described by a Fourier model.
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Dióxido de Carbono/metabolismo , Metano/metabolismo , Áreas Alagadas , Ritmo Circadiano , Panamá , Estações do AnoRESUMO
The extraction of sulphur produces a hematite-rich waste, known as roasted pyrite ash, which contains significant amounts of environmentally sensitive elements in variable concentrations and modes of occurrence. Whilst the mineralogy of roasted pyrite ash associated with iron or copper mining has been studied, as this is the main source of sulphur worldwide, the mineralogy, and more importantly, the characterization of submicron, ultrafine and nanoparticles, in coal-derived roasted pyrite ash remain to be resolved. In this work we provide essential data on the chemical composition and nanomineralogical assemblage of roasted pyrite ash. XRD, HR-TEM and FE-SEM were used to identify a large variety of minerals of anthropogenic origin. These phases result from highly complex chemical reactions occurring during the processing of coal pyrite of southern Brazil for sulphur extraction and further manufacture of sulphuric acid. Iron-rich submicron, ultrafine and nanoparticles within the ash may contain high proportions of toxic elements such as As, Se, U, among others. A number of elements, such as As, Cr, Cu, Co, La, Mn, Ni, Pb, Sb, Se, Sr, Ti, Zn, and Zr, were found to be present in individual nanoparticles and submicron, ultrafine and nanominerals (e.g. oxides, sulphates, clays) in concentrations of up to 5%. The study of nanominerals in roasted pyrite ash from coal rejects is important to develop an understanding on the nature of this by-product, and to assess the interaction between emitted nanominerals, ultra-fine particles, and atmospheric gases, rain or body fluids, and thus to evaluate the environmental and health impacts of pyrite ash materials.
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Cinza de Carvão/análise , Poluentes Ambientais/análise , Minerais/análise , Nanopartículas/análise , Material Particulado/análise , Brasil , Monitoramento Ambiental , Compostos Férricos/análise , Ferro/química , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Sulfetos/química , Ácidos Sulfúricos/químicaRESUMO
Orexins (hypocretins) are peptide neurotransmitters produced by a small group of neurons located exclusively in the lateral hypothalamus (LH). Orexins modulate arousal, and as a result, have profound effects on feeding behavior and the sleep-wake cycle. Loss of orexin producing neurons leads to a narcoleptic phenotype, characterized by sudden transitions from vigilance to rapid eye movement (REM) sleep (direct transition to REM, DREM) observed in electroencephalogram (EEG) and electromyogram (EMG) recordings. In this study, we demonstrate that mice lacking the basic helix-loop-helix transcription factor O/E3 (also known as ebf2) have a decrease in orexin-producing cells in the LH, in addition to a severely impaired orexinergic innervation of the pons. These changes in the orexinergic circuit of O/E3-null animals induce a narcoleptic phenotype, similar to the one arising in orexin-deficient and orexin-ataxin-3 mice. Taken together, our results suggest that O/E3 plays a central role during the establishment of a functional orexinergic circuit by controlling the expression of essential hypothalamic neurotransmitter and the correct development of the nerve fibers arising from the hypothalamus. This is the first report regarding the narcolepsy-cataplexy syndrome in O/E3-null mice, which adds the importance of transcription factors in the regulation of neural subpopulations that control the sleep-wake cycle.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Narcolepsia/genética , Narcolepsia/fisiopatologia , Animais , Nível de Alerta/efeitos dos fármacos , Encéfalo/patologia , Catalepsia , Contagem de Células , Ritmo Circadiano/fisiologia , Modelos Animais de Doenças , Eletroencefalografia , Eletromiografia , Regulação da Expressão Gênica/genética , Cobaias , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Narcolepsia/tratamento farmacológico , Narcolepsia/patologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Neuropeptídeos/uso terapêutico , Neurotransmissores/uso terapêutico , Orexinas , Transativadores/genética , Transativadores/metabolismoRESUMO
Objective: To evaluate the effects of a nutritional intervention focused on the improvement of clinical status and the prognosis of heart failure patients. Methods: A 12-mo randomized controlled study in 203 heart failure (HF) patients assigned to intervention (IG, n=84) or control group (CG, n=119). Patients in the IG received a sodium (2000 to 2400 mg/d) and fluid (<1500 ml/d) restricted diet. CG received general nutritional recommendations. Body composition, clinical status, hospitalization and time of survival were evaluated. Results: At the end of follow-up, urinary sodium excretion decreased 16,4 percent in the IG vs. an 8,8 percent increase in the CG (p<0,05). Extra cellular water decreased 1,4 percent in the IG vs. a 1¡2 percent increase in the CG (p=0,03). In addition, decrease percentage of fatigue was significant and higher in the IG that in the CG, and a significant increase in the ejection fraction for the IG vs. CG (49,6 percent vs. 5,0 percent, p=0,001), among systolic HF patients was found. Amount of hospitalizations and time of survival tended to be better in the IG. Conclusion: A nutritional intervention with restriction of sodium and fluid was proved to be beneficial since had positive effects in clinical status in HF patients.
Objetivo: Evaluar el efecto de una intervención nutricional sobre el estado clínico y el pronóstico de pacientes con insuficiencia cardiaca (IC). Métodos: Doscientos tres pacientes con IC fueron aleatorizados al grupo con intervención (GI, n=84) o al control (GC, n=119) y seguidos por 12 meses. El GI recibió una dieta con restricción de sodio (2000 a 2400 mg/d) y líquidos (<1500 ml/d) y el GC recomendaciones nutricionales generales. Se evaluó la composición corporal, el estado clínico, hospitalizaciones y sobrevida. Resultados: Al término del seguimiento, la excreción urinaria de sodio disminuyó 16,4 por ciento en el GI vs. un aumento de 8,8 por ciento en el GC (p<0,05). El agua extracellular disminuyó 1,4 por ciento en el GI vs. 1,2 por ciento de aumento en el GC (p=0,03). Asimismo, el porcentaje de reducción de fatiga fue significativo para el GI, no así para el GC; también se observó, entre los pacientes con IC sistólica, un aumento significativamente mayor en la fracción de expulsión para el GI vs. CG (49,6 por ciento vs. 5,0 por ciento, p=0,001). El número de hospitalizaciones y el tiempo de sobrevida tuvieron una tendencia a ser mejor en el GI. Conclusión: Una intervención nutricional con restricción de sodio y líquidos mostró tener un impacto favorable en el estado clínico de pacientes con IC.
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Humanos , Dieta Hipossódica , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Ingestão de Líquidos/fisiologiaRESUMO
Endogenous cannabinoids or endocannabinoids are lipid molecules that have a variety of biological actions, most notably via activation of the cannabinoid receptors. The family of endocannabinoids includes arachidonoylethanolamide (ANA) which modulates different behaviors, such as sleep. However, it is unknown whether pharmacological elevation of ANA endogenous levels might induce sleep. VDM 11 [(5 Z,8 Z,11 Z,14 Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide] is commonly used as an inhibitor of ANA cellular uptake, and thereby to potentiate its actions. In this study we have examined whether VDM-11 exerts any effect on the sleep-wake cycle and c-Fos expression in brain areas. When assayed alone in rats, VDM-11 (10 or 20 microg/5 microL, i.c.v.) at the beginning of the lights-off period, reduced wakefulness and increased sleep. The CB(1) cannabinoid receptor antagonist, SR141716A, partially reversed the effects of VDM-11 on sleep. Additionally, VDM-11 enhanced c-Fos expression in sleep-related brain areas such as the anterior hypothalamic area, paraventricular thalamic nucleus, and pedunculopontine tegmental nucleus. It is concluded that VDM-11 displays sleep-inducing properties and these effects slightly, albeit significantly, are reversed using SR141716A. Furthermore, c-Fos data suggest a possible underlying neuroanatomical substrate of the sleep-inducing properties of VDM-11. We report evidence suggesting that VDM-11 might be considered for the development of new pharmacological and pharmaceutical approaches to treat sleep disorders such as insomnia.
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Ácidos Araquidônicos/farmacologia , Química Encefálica/efeitos dos fármacos , Química Encefálica/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos/genética , Alcamidas Poli-Insaturadas/farmacologia , Sono/efeitos dos fármacos , Animais , Ácidos Araquidônicos/administração & dosagem , Antagonistas de Receptores de Canabinoides , Eletroencefalografia/efeitos dos fármacos , Endocanabinoides , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/efeitos dos fármacos , Rimonabanto , Fases do Sono/efeitos dos fármacosRESUMO
INTRODUCTION: The discovery that new neurons continue to be generated in the adult brain has modified the concept of brain plasticity and has brought to light new mechanisms that ensure the homeostasis of the nervous system. DEVELOPMENT: Neurogenesis, that is to say, the process involving the generation of new neurons, has been shown to occur in the hippocampus and in the olfactory bulb in adult mammals, which suggests that neuronal stem cells persist throughout the entire lifespan. The primary precursors have been identified in specialised regions called neurogenic niches. Interestingly, the cells that give rise to the new neurons in the adult brain express markers for glial cells, a cell lineage that is a long way from that of neurons. Studies conducted during the development of the brain have shown that radial glial cells not only give rise to astrocytes but also neurons, oligodendrocytes and ependymal cells. In addition, it is known that radial glial cells are also the precursors of neuronal stem cells in the adult brain. CONCLUSIONS: Overall, these data support the idea that stem cells develop from a neuroepithelial-glial radial-astrocytic lineage. Thus, identifying the primary precursors, both in the developing brain and in the adult brain, is essential to understand the functioning of the nervous system and, from there, to develop strategies for neuronal replacement in the adult brain when needed.
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Encéfalo/crescimento & desenvolvimento , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Células-Tronco/fisiologia , Adulto , Animais , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Diferenciação Celular/fisiologia , Linhagem da Célula , Movimento Celular/fisiologia , Homeostase , Humanos , Neuroglia/citologia , Neuroglia/fisiologia , Neurônios/citologia , Bulbo Olfatório/citologia , Bulbo Olfatório/fisiologia , Células-Tronco/citologiaAssuntos
Humanos , Masculino , Feminino , Ecologia/classificação , Ecologia/educação , Ecologia/tendênciasAssuntos
Masculino , Feminino , Humanos , Ecologia/classificação , Ecologia/educação , Ecologia/tendênciasAssuntos
Masculino , Feminino , Humanos , Animais , Ecologia/educação , Ecologia/métodos , Ecologia/tendênciasAssuntos
Humanos , Animais , Masculino , Feminino , Ecologia/educação , Ecologia/métodos , Ecologia/tendênciasRESUMO
Brazilian peppertree (Schinus terebinthifolius) is a woody perennial that has invaded much of Florida. This native of northeastern Argentina, Paraguay, and Brazil was brought as an ornamental to both the west and east coasts of Florida at the end of the 19th century. It was recorded as an invader of natural areas in the 1950s, and has since extended its range to cover over 280 000 ha. Our goals were to understand the history of this invasion, as one step toward understanding why this exotic was so successful, and ultimately to improve development of biological control agents. We sampled plants from the native and exotic ranges, particularly Florida, and genotyped these individuals at nuclear and chloroplast loci. Nuclear microsatellite and cpDNA loci reveal strong genetic population structure consistent with limited dispersal in the introduced and native ranges. Bayesian clustering of microsatellite data separates the east and west coast plants in Florida into distinct populations. The two chloroplast haplotypes found in Florida are also concordant with this separation: one predominates on the east coast, the other on the west coast. Analysis of samples collected in South America shows that haplotypes as distinct as the two in Florida are unlikely to have come from a single source population. We conclude that the genetic evidence supports two introductions of Brazilian peppertree into Florida and extensive hybridization between them. The west coast genotype likely came from coastal Brazil at about 27 degrees south, whereas the east coast genotype probably originated from another, as yet unidentified site. As a result of hybridization, the Florida population does not exhibit low genetic variation compared to populations in the native range, possibly increasing its ability to adapt to novel environments. Hybridization also has important consequences for the selection of biocontrol agents since it will not be possible to identify closely co-adapted natural enemies in the native range, necessitating more extensive host testing.
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Anacardiaceae/genética , DNA de Cloroplastos/genética , Repetições de Microssatélites/genética , Filogenia , Argentina , Brasil , Análise por Conglomerados , Florida , Variação Genética , Haplótipos , Havaí , Hibridização Genética , Paraguai , Texas , Ilhas Virgens AmericanasRESUMO
The objective of this study was to assess the predictive capacity of the biotic ligand model (BLM) for acute copper toxicity to daphnids as applied to a number of freshwaters from Chile and to synthetic laboratory-prepared waters. Thirty-seven freshwater bodies were sampled, chemically characterized, and used to determine the copper concentration associated with the 50% of mortality (LC50) for Daphnia magna, Daphnia pulex, and Daphnia obtusa (native to Chile). The data were then used to run three versions of the acute copper BLM, and the predicted LC50s were compared to the observed ones. The same was done with synthetic assay media at various hardness and dissolved organic carbon (DOC) levels. The BLM versions differed in the affinity constants for some biotic ligand-ion pairs, stability constants for inorganic Cu complexes, and assumptions regarding Cu binding to DOC. All three versions showed a high degree of predictive performance, mostly within a twofold range of observed toxicity values. The D. obtusa data set was used to compare water quality criteria (WQC) derived from the observed toxicity values with those derived from either the BLM or the U.S. Environmental Protection Agency (U.S. EPA) procedure. For most low DOC waters, the three procedures generated similar WQCs. For the high-DOC waters, the EPA-derived criteria were significantly lower, that is, greatly overprotective. The results are also discussed in terms of the validation of the BLM for regulatory use.
Assuntos
Cobre/toxicidade , Daphnia/efeitos dos fármacos , Ligantes , Poluentes da Água/toxicidade , Água/química , Animais , Carbono/análise , Carbono/química , Chile , Cobre/metabolismo , Daphnia/metabolismo , Modelos Biológicos , Compostos Orgânicos/química , Valor Preditivo dos Testes , Testes de Toxicidade Aguda/métodos , Poluentes da Água/metabolismoRESUMO
BACKGROUND: The majority of medicines prescribed for children are prescribed in primary care for common acute and chronic conditions. This is in contrast to prescribing in secondary care where the population of children admitted is small but where a large number of different medicines are prescribed to treat more serious and less common conditions. METHODS: Data on prescribing was extracted from the General Practice Administration System for Scotland (GPASS) for the year November 1999 to October 2000 and prescribing patterns for children aged 0-16 years expressed as percentages. A comparison of age specific consultations for asthma, as an example of a common paediatric condition, was also made between two separate general practice data sets, the General Practice Research Database (GRPD) and the continuous morbidity recording (CMR) subset of GPASS. RESULTS: Of 214 medicines investigated for unlicensed and off-label prescribing no unlicensed prescribing was identified. Off-label prescribing due to age was most common among younger and older children. The most common reasons for off-label prescriptions were, in order of frequency, lower than recommended dose, higher than recommended dose, below the recommended age, and unlicensed formulation. Age and gender specific consultations for asthma were similar in the two representative databases, GPRD and CMR, both showing disappearance of the male predominance in the teenage years. CONCLUSIONS: Large primary care data sets available within a unified health care system such as the UK National Health Service (NHS) are likely to be broadly compatible and produce similar results. The prescribing of off-label medicines to children is common in primary care, most commonly due to prescribing out with the recommended dosage regimen.