RESUMO
In the present work, a novel cross-linked polymer was synthesized though the anionic polymerization of cyanoacrylate with moisture as an initiator, methylene-bis-acrylamide as a cross-linker, and linseed oil as a spacer. Two layers of the synthesized polymer was coated over polyacrylamide for its homogenous impregnation in Class-G cement slurry for the synthesis of cement core. Fourier Transformation Infrared spectroscopy and X-Ray diffraction spectrum of the synthesized polymer and cement core were obtained to investigate the presence of different functional groups and phases. Moreover, the morphologies of the dual-encapsulated polyacrylamide was observed through scanning electron microscopy. Furthermore, the water-absorption capacity of the synthesized dual-encapsulated polyacrylamide in normal and saline conditions were tested. A cement core impregnated with 16% of dosage of dual-encapsulated polyacrylamide possesses an effective self-healing capability during the water-flow test. Moreover, the maximum linear expansion of the cement core was observed to be 26%. Thus, the impregnation of dual-encapsulated polyacrylamide in cement slurry can exhibit a superior self-healing behavior upon water absorption in an oil well.
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Multiple sclerosis (MS) is a neuro-inflammatory and demyelinating disease. Downregulation of neuronal mitochondrial gene expression and activity have been reported in several studies of MS. We have previously shown that hemoglobin-ß (Hbb) signals to the nucleus of neurons and upregulates H3K4me3, a histone mark involved in regulating cellular metabolism and differentiation. The present study was undertaken to evaluate the effect of erythropoietin (EPO) on the upregulation of hemoglobin and mitochondrial-associated neuroprotection. We found that administering EPO (5000 IU/kg intraperitoneally) to mice upregulated brain Hbb expression, levels of H3K4me3, expression of mitochondrial complex III, complex V, and mitochondrial respiration. We also found that the neuronal mitochondrial metabolite N-acetylaspartate (NAA), a marker of neuronal mitochondrial activity, was increased with EPO treatment. Further, we measured the effects of EPO on preventing mitochondrial deficits in the cuprizone toxic demyelinating mouse model of MS. We found that EPO prevented cuprizone-mediated decreases in Hbb, complex III, and NAA. Our data suggest that EPO mediated regulation of Hbb supports neuronal energetics and may provide neuroprotection in MS and other neurodegenerative diseases where a dysfunction of mitochondria contributes to disease.
Assuntos
Encéfalo/metabolismo , Eritropoetina/farmacologia , Hemoglobinas/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Respiração Celular/efeitos dos fármacos , Cuprizona , Modelos Animais de Doenças , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Masculino , Metilação , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Modelos Biológicos , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Proteína Básica da Mielina/metabolismo , Bainha de Mielina/metabolismo , Neurônios/efeitos dos fármacosRESUMO
We report a significant reduction in plasma methionine concentrations in relapse remitting multiple sclerosis (MS) patients compared to controls. In vivo studies demonstrate that changes in peripheral methionine levels in mice can regulate histone H3 methylation and expression of DNA methyltransferase 3A (DNMT3A) centrally, in the cerebral cortex. Therefore, we propose that decreases in circulating methionine represent one of the earliest manifestations of dysregulated methionine metabolism in MS with potential impacts on both histone H3 and DNA methylation in the central nervous system.
Assuntos
Córtex Cerebral/metabolismo , Metionina/metabolismo , Esclerose Múltipla Recidivante-Remitente/metabolismo , Adulto , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , DNA Metiltransferase 3A , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metionina/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologiaRESUMO
OBJECTIVE: To compare the neurodevelopmental outcomes at 18 to 21 months corrected age (CA) of infants born at <29 weeks that received room air, an intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. STUDY DESIGN: In this retrospective cohort study, we compared neonatal and neurodevelopmental outcomes at 18 to 21 months CA among inborn infants born before 29 weeks' gestation that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. RESULTS: Of 1509 infants, 445 received room air, 483 received intermediate oxygen concentrations and 581 received 100% oxygen. Compared to infants that received room air, the primary outcome of death or neurodevelopmental impairment (NDI) was not different in intermediate oxygen (adjusted odds ratio (aOR) 1.01; 95% confidence interval (CI) 0.77, 1.34) or 100% oxygen (aOR 1.03; 95% CI 0.78, 1.35). Compared to room air, there was no difference in odds of death or severe NDI in intermediate oxygen (aOR 1.14; 95% CI 0.82, 1.58) or 100% oxygen group (aOR 1.22; 95% CI 0.90, 1.67). The odds of severe NDI among survivors were significantly higher in infants that received 100% oxygen as compared to room air (aOR 1.57, 95% CI 1.05, 2.35). CONCLUSIONS: We observed no significant difference in the primary composite outcomes of death or NDI and death or severe NDI at 18 to 21 months CA between infants that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. However, use of 100% oxygen was associated with increased odds of severe NDI among survivors as compared to room air.
Assuntos
Transtornos do Neurodesenvolvimento/epidemiologia , Oxigenoterapia , Ressuscitação/efeitos adversos , Ressuscitação/métodos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/mortalidade , Unidades de Terapia Intensiva Neonatal , Transtornos do Neurodesenvolvimento/etiologia , Ressuscitação/mortalidade , Estudos Retrospectivos , Fatores de RiscoRESUMO
The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination. To test this hypothesis, we performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) to identify changes in myelin lipid composition in postmortem MS brains and in NAT8L knockout (NAT8L-/-) mice which do not synthesize NAA. We found reduced levels of sphingomyelin in MS normal appearing white matter that mirrored decreased levels of NAA. We also discovered decreases in the amounts of sphingomyelin and sulfatide lipids in the brains of NAT8L-/- mice compared to controls. Metabolomic analysis of primary cultures of oligodendrocytes treated with NAA revealed increased levels of α-ketoglutarate, which has been reported to regulate histone demethylase activity. Consistent with this, NAA treatment resulted in alterations in the levels of histone H3 methylation, including H3K4me3, H3K9me2, and H3K9me3. The H3K4me3 histone mark regulates cellular energetics, metabolism, and growth, while H3K9me3 has been linked to alterations in transcriptional repression in developing oligodendrocytes. We also noted the NAA treatment was associated with increases in the expression of genes involved in sulfatide and sphingomyelin synthesis in cultured oligodendrocytes. This is the first report demonstrating that neuronal-derived NAA can signal to the oligodendrocyte nucleus. These data suggest that neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to support or maintain myelination.
Assuntos
Ácido Aspártico/análogos & derivados , Sistema Nervoso Central/patologia , Histonas/metabolismo , Esclerose Múltipla/patologia , Bainha de Mielina/patologia , Neurônios/efeitos dos fármacos , Acetiltransferases/genética , Acetiltransferases/metabolismo , Animais , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Células Cultivadas , Cromatografia Líquida , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Histonas/genética , Humanos , Ácidos Cetoglutáricos/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oligodendroglia , Mudanças Depois da Morte , Espectrometria de Massas em TandemRESUMO
OBJECTIVES: To compare short- and long-term neurodevelopmental outcomes at 3 years of corrected age of preterm infants cared for by 24-hour in-house staff neonatologists and those cared for by staff neonatologists during daytime only. METHODS: Retrospective analysis of prospectively collected follow-up data on all nonanomalous preterm infants from 1998 to 2004 excluding year 2001 as a washout period. Infants were divided into two groups based on care provided by staff neonatologists: 24-hour in-house coverage (24-hour coverage 1998-2000) and daytime coverage (day coverage 2002-2004). Short- and long-term outcomes were compared. RESULTS: A total of 387 (78%) of the screened infants were included. Twenty-four-hour coverage (n=179) and day coverage (n=208) groups had a median birth weight (BW) of 875 g (range 470-1250) and 922 g (480-1530; P=0.028), respectively, and both had a median gestational age of 27 weeks. In the day coverage group, a smaller proportion of mothers had chorioamnionitis (20% vs. 30%; P=0.025), received less antibiotics (62% vs. 73%; P=0.023), and infants had fewer cases of confirmed sepsis (14% vs. 23%; P=0.022). In the day coverage group, a larger number of infants had respiratory distress syndrome (87% vs. 77%; P=0.011) and required prolonged mechanical ventilation (median 31 vs. 21 days; P=0.002). The incidence of major neurodevelopmental impairment was not significantly different between the two groups (odds ratio 0.76; 95% confidence interval 0.34-1.65). CONCLUSIONS: Duration of mechanical ventilation was reduced with 24-hour in-house coverage by staff neonatologists. However, 24-hour coverage was not associated with any difference in neurodevelopmental (ND) outcomes at 3-year corrected age.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias Urogenitais/tratamento farmacológico , Austrália/epidemiologia , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Nova Zelândia/epidemiologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/epidemiologiaRESUMO
Data from registries at four major public hospitals in South Australia indicate increased 5-year disease-specific survivals for colorectal cancer from 48% to 63% between 1980-1986 and 2005-2010. For 80+ year olds, the increase was smaller, from 47% to 52%. Risk of case fatality halved overall, adjusting for age, gender, stage, differentiation and sub-site. Patients aged 80+ years had a lower risk reduction of about a third (hazards ratio: 0.69; 95% confidence limits, 0.52-0.92). Percentages having surgery and other specified treatments were lower for 80+ year olds than younger cases, although increases in treatment intensity occurred in this age range during 1980-2010, as seen in younger ages, in accordance with guidelines. The study illustrates the important feedback clinical registries can provide to clinicians on care patterns and outcomes in their hospital settings. Feedback can be the subject of local deliberations on how to achieve the best outcomes, including in the elderly by considering the best trade-offs between optimal cancer care and accommodations for co-morbidity and frailty. Clinical registry data can be used in comparative effectiveness research in local settings where there are sufficient case numbers.
Assuntos
Neoplasias do Colo/terapia , Neoplasias Retais/terapia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Feminino , Hospitais Públicos/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/mortalidade , Austrália do SulRESUMO
Recent studies have reported that the virulence factors (VFs) were detected more frequently in amoxicillin-clavulanate (AMC) susceptible clinical isolates of Escherichia coli. Here, we have evaluated the relationship between VFs and AMC-resistance phenotype in clinical isolates of Y. enterocolitica biovar 1A. The presence/absence of VFs was compared with their minimum inhibitory concentrations for AMC in strains of two serovars. We observed that the strains of the serovar O: 6, 30-6, 31 showed a similar relationship between the number of VFs and resistance to clavulanic acid as in E. coli but not of serovar O: 6, 30. Variations in the promoters/complete coding sequences (CCDSs) of ß-lactamase gene (bla A) or the serological characteristics could not account for unusual susceptibility to AMC displayed by the strains of the serovar O: 6, 30. Therefore, we speculate that since the clinical strains of serovar O: 6, 30-6, 31 originated from the environment they were less exposed to antibiotics compared to clinical strains of serovar O: 6, 30. Thus, AMC susceptibility seems to be influenced by factors other than serotypes or promoters/CCDS of ß-lactamase genes.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Fatores de Virulência/análise , Yersinia enterocolitica/efeitos dos fármacos , Yersinia enterocolitica/patogenicidade , Resistência beta-Lactâmica , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , Fatores de Virulência/genética , Yersiniose/microbiologia , Yersinia enterocolitica/isolamento & purificação , beta-Lactamases/genéticaRESUMO
This study investigated organic micropollutant (OMP) biodegradation rates in laboratory-scale soil columns simulating river bank filtration (RBF) processes. The dosed OMP mixture consisted of 11 pharmaceuticals, 6 herbicides, 2 insecticides and 1 solvent. Columns were filled with soil from a RBF site and were fed with four different organic carbon fractions (hydrophilic, hydrophobic, transphilic and river water organic matter (RWOM)). Additionally, the effect of a short-term OMP/dissolved organic carbon (DOC) shock-load (e.g. quadrupling the OMP concentrations and doubling the DOC concentration) on OMP biodegradation rates was investigated to assess the resilience of RBF systems. The results obtained in this study imply that - in contrast to what is observed for managed aquifer recharge systems operating on wastewater effluent - OMP biodegradation rates are not affected by the type of organic carbon fraction fed to the soil column, in case of stable operation. No effect of a short-term DOC shock-load on OMP biodegradation rates between the different organic carbon fractions was observed. This means that the RBF site simulated in this study is resilient towards transient higher DOC concentrations in the river water. However, a temporary OMP shock-load affected OMP biodegradation rates observed for the columns fed with the river water organic matter (RWOM) and the hydrophilic fraction of the river water organic matter. These different biodegradation rates did not correlate with any of the parameters investigated in this study (cellular adenosine triphosphate (cATP), DOC removal, specific ultraviolet absorbance (SUVA), richness/evenness of the soil microbial population or OMP category (hydrophobicity/charge).
Assuntos
Modelos Teóricos , Compostos Orgânicos/análise , Rios/química , Microbiologia do Solo , Solo/química , Poluentes Químicos da Água/análise , Biodegradação Ambiental , Carbono/química , Filtração , Água Doce/química , Água Subterrânea/química , Solubilidade , Águas Residuárias/químicaRESUMO
This study investigated relationships between OMP biodegradation rates and the functional groups present in the chemical structure of a mixture of 31 OMPs. OMP biodegradation rates were determined from lab-scale columns filled with soil from RBF site Engelse Werk of the drinking water company Vitens in The Netherlands. A statistically significant relationship was found between OMP biodegradation rates and the functional groups of the molecular structures of OMPs in the mixture. The OMP biodegradation rate increased in the presence of carboxylic acids, hydroxyl groups, and carbonyl groups, but decreased in the presence of ethers, halogens, aliphatic ethers, methyl groups and ring structures in the chemical structure of the OMPs. The predictive model obtained from the lab-scale soil column experiment gave an accurate qualitative prediction of biodegradability for approximately 70% of the OMPs monitored in the field (80% excluding the glymes). The model was found to be less reliable for the more persistent OMPs (OMPs with predicted biodegradation rates lower or around the standard error=0.77d(-1)) and OMPs containing amide or amine groups. These OMPs should be carefully monitored in the field to determine their removal during RBF.
Assuntos
Modelos Lineares , Poluentes Químicos da Água , Biodegradação Ambiental , Filtração , Rios/química , Solo/química , Microbiologia do Solo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Poluentes Químicos da Água/metabolismoRESUMO
This study investigated the redox dependent removal and adaptive behaviour of a mixture of 15 organic micropollutants (OMPs) in laboratory-scale soil columns fed with river water. Three separate pilot systems were used consisting of: (1) two columns, (2) ten columns and (3) twenty two columns to create oxic, suboxic (partial nitrate removal) and anoxic (complete nitrate removal). The pilot set-up has some unique features--it can simulate fairly long residence times (e.g., 45 days using the 22 column system) and reduced conditions developed naturally within the system. Dimethoate, diuron, and metoprolol showed redox dependent removal behaviour with higher biodegradation rates in the oxic zone compared to the suboxic/anoxic zone. The redox dependent behaviour of these three OMPs could not be explained based on their physico-chemical properties (hydrophobicity, charge and molecular weight) or functional groups present in the molecular structure. OMPs that showed persistent behaviour in the oxic zone (atrazine, carbamazepine, hydrochlorothiazide and simazine) were also not removed under more reduced conditions. Adaptive behaviour was observed for five OMPs: dimethoate, chloridazon, lincomycin, sulfamethoxazole and phenazone. However, the adaptive behaviour could not be explained by the physico-chemical properties (hydrophobicity, charge and molecular weight) investigated in this study and only rough trends were observed with specific functional groups (e.g. ethers, sulphur, primary and secondary amines). Finally, the adaptive behaviour of OMPs was found to be an important factor that should be incorporated in predictive models for OMP removal during river bank filtration.
Assuntos
Modelos Químicos , Rios/química , Poluentes Químicos da Água/análise , Biodegradação Ambiental , Filtração , OxirreduçãoRESUMO
This study investigated sorption and biodegradation behaviour of 20 organic micropollutants (OMPs) in lab-scale columns filled with two types of soil (fed with the same water quality) simulating river bank filtration (RBF) under oxic conditions. Retardation factors and OMP biodegradation rates were similar for the two soils that were characterised by a different cationic exchange capacity, organic matter and sand/silt/clay content. This result was supported by the microbial community composition (richness, evenness) of the two soils that became more similar as a result of feeding both columns with the same water quality. This indicates that microbial community composition and thereby OMP removal in soils is primarily determined by the composition of the aqueous phase (organic matter quantity and quality, nutrients) rather than the soil phase. These results indicate that different RBF sites located along the same river may show similar OMP removal (in case of similar water quality and residence time). CAPSULE: This study shows that the microbial community composition and thus OMP removal is primarily determined by the aqueous phase (water quality) rather than the soil phase.
Assuntos
Microbiologia do Solo , Poluentes do Solo/análise , Solo/química , Biodegradação Ambiental , Variação GenéticaRESUMO
OBJECTIVE: To compare neonatal outcomes of preterm infants (born at <32 weeks' gestation) with focal/spontaneous intestinal perforation (SIP), necrotizing enterocolitis (NEC)-related perforation, NEC without perforation or no NEC/perforation. STUDY DESIGN: Retrospective cohort study of 17,426 infants admitted to Canadian neonatal intensive care units during 2010 to 2013. The primary outcome was a composite of mortality or morbidity (bronchopulmonary dysplasia, severe retinopathy, periventricular leukomalacia or nosocomial infection). Association of intestinal perforation with neonatal outcome was evaluated using multivariate logistic regression. RESULT: SIP was present in 178 (1.0%) infants, NEC-related perforation in 246 (1.4%) and NEC without perforation in 538 (3.1%). Any intestinal perforation was associated with higher odds of the composite outcome (adjusted odds ratio (AOR): 8.21, 95% confidence interval (95% CI) 6.26 to 10.8); however, the odds were significantly lower for focal/SIP compared with NEC-related perforation (AOR: 0.29, 95% CI 0.17 to 0.51). CONCLUSION: Of the two types of intestinal perforation, NEC-related perforation was associated with the highest risk of an adverse neonatal outcome.
Assuntos
Infecção Hospitalar/epidemiologia , Enterocolite Necrosante/diagnóstico , Lactente Extremamente Prematuro , Doenças do Prematuro/classificação , Doenças do Prematuro/epidemiologia , Perfuração Intestinal/diagnóstico , Canadá , Enterocolite Necrosante/complicações , Feminino , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
AIM: To gain ideas and information from healthcare providers to optimize the education and clinical practices of nurses caring for sick or at-risk newborns in India. BACKGROUND: Improving infant survival has been identified as a Millennium Development Goals; however, India still faces many challenges with 3.1 million neonatal deaths and 2.6 million stillbirths annually. Skilled nursing care has been associated with decreased morbidity and mortality in newborns. However, core competencies in newborn care education and training are lacking for nurses. METHODS: Qualitative data were collected from 12 focus groups with 101 newborn care providers from three areas of India as well as from a 2-day stakeholders' meeting. Data analysis was undertaken using descriptive and thematic content analysis. RESULTS: Perceived challenges included limited manpower and high nurse turnover, lack of access to evidence-based orientation to newborn care and problems with access to appropriate learner-based, neonatal training. Relevant, ongoing education opportunities, led by nursing leaders were identified to be important solutions. CONCLUSION: Findings provide insight into the current healthcare system in India with specific reference to the nursing care of at-risk newborns. There is a lack of existing resources to provide standardized and specific orientation curricula for nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Policy makers in health and education need to: support and enact learner-based orientation and continuing educational opportunities as well as ongoing competency-based education programmes; encourage nurse leader involvement and support; and provide sustainable system-related supports. Nurses and other health providers need to work together to influence government policy.
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This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity.
Assuntos
Terapia de Reposição Hormonal/métodos , Neoplasias Embrionárias de Células Germinativas/sangue , Qualidade de Vida , Neoplasias Testiculares/sangue , Testosterona/deficiência , Adulto , Austrália/epidemiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Nova Zelândia/epidemiologia , Prevalência , Estudos Prospectivos , Taxa de Sobrevida/tendências , Sobreviventes , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/epidemiologia , Adulto JovemAssuntos
Povo Asiático/psicologia , Atividades de Lazer/psicologia , Atividade Motora , Comportamento Sedentário/etnologia , Povo Asiático/estatística & dados numéricos , Estudos Transversais , Planejamento Ambiental/estatística & dados numéricos , Humanos , Índia , Relações Interpessoais , Masculino , Motivação , Meio Social , Inquéritos e Questionários , Fatores de Tempo , População Urbana/estatística & dados numéricos , Local de Trabalho/estatística & dados numéricosRESUMO
BACKGROUND: This Australian single-arm, multicenter, phase II trial evaluated feasibility, tolerability and activity of accelerated bleomycin, etoposide and cisplatin (BEP) as first-line chemotherapy for metastatic germ cell tumours. PATIENTS AND METHODS: Patients were planned to receive cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) days 1-5, and pegfilgrastim 6 mg day 6, all repeated every 2 weeks for four cycles (three cycles for good prognosis). Bleomycin was given at 30 000 IU weekly to a total of 12 doses (9 doses for good prognosis). Primary end point was feasibility, defined as the proportion of patients able to complete the etoposide and cisplatin components of BEP and be eligible to receive a fourth cycle of BEP by day 50. RESULTS: Twelve poor, 16 intermediate and 15 good prognosis (n = 43) eligible patients were enrolled. Two patients aged >40 years were ineligible and excluded from analyses. The regimen was feasible in 86%, not feasible in 7% and not assessable in 7% of patients. Most common grade 3/4 adverse events were non-neutropenic infection (16%) and febrile neutropenia (12%). Complete response (CR) to chemotherapy and surgery was achieved in 33% poor-prognosis, 81% intermediate-prognosis and 100% good-prognosis patients. At median follow-up of 27 months (range 6-42), the 2-year progression-free survival was 50% for poor-prognosis, 94% for intermediate-prognosis and 92% for good-prognosis patients. CONCLUSION: Accelerated BEP is feasible and tolerable. Efficacy data appear to be promising. This trial and a similar UK study provide the rationale for a randomised trial comparing accelerated versus standard BEP. Australian New Zealand Clinical Trials Registry Registration number. ACTRN 12607000294459.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/secundário , Prognóstico , Neoplasias Testiculares/patologia , Resultado do Tratamento , Adulto JovemRESUMO
This study investigated sorption and biodegradation behaviour of 14 organic micropollutants (OMP) in soil columns representative of the first metre (oxic conditions) of the river bank filtration (RBF) process. Breakthrough curves were modelled to differentiate between OMP sorption and biodegradation. The main objective of this study was to investigate if the OMP biodegradation rate could be related to the physico-chemical properties (charge, hydrophobicity and molecular weight) or functional groups of the OMPs. Although trends were observed between charge or hydrophobicity and the biodegradation rate for charged compounds, a statistically significant linear relationship for the complete OMP mixture could not be obtained using these physico-chemical properties. However, a statistically significant relationship was obtained between biological degradation rates and the OMP functional groups. The presence of ethers and carbonyl groups will increase biodegradability, while the presence of amines, ring structures, aliphatic ethers and sulphur will decrease biodegradability. This predictive model based on functional groups can be used by drinking water companies to make a first estimate whether a newly detected compound will be biodegraded during the first metre of RBF or that additional treatment is required. In addition, the influence of active and inactive biomass (biosorption), sand grains and the water matrix on OMP sorption was found to be negligible under the conditions investigated in this study. Retardation factors for most compounds were close to 1, indicating mobile behaviour of these compounds during soil passage. Adaptation of the biomass towards the dosed OMPs was not observed for a 6 month period, implying that new developed RBF sites might not be able to biodegrade compounds such as atrazine and sulfamethoxazole in the first few months of operation.