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1.
Circulation ; 140(18): 1463-1476, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31524498

RESUMO

BACKGROUND: Outcome trials in patients with type 2 diabetes mellitus have demonstrated reduced hospitalizations for heart failure (HF) with sodium-glucose co-transporter-2 inhibitors. However, few of these patients had HF, and those that did were not well-characterized. Thus, the effects of sodium-glucose co-transporter-2 inhibitors in patients with established HF with reduced ejection fraction, including those with and without type 2 diabetes mellitus, remain unknown. METHODS: DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) was an investigator-initiated, multi-center, randomized controlled trial of HF patients with left ventricular ejection fraction ≤40%, New York Heart Association (NYHA) class II-III, estimated glomerular filtration rate ≥30 mL/min/1.73m2, and elevated natriuretic peptides. In total, 263 patients were randomized to dapagliflozin 10 mg daily or placebo for 12 weeks. Dual primary outcomes were (1) mean NT-proBNP (N-terminal pro b-type natriuretic peptide) and (2) proportion of patients with ≥5-point increase in HF disease-specific health status on the Kansas City Cardiomyopathy Questionnaire overall summary score, or a ≥20% decrease in NT-proBNP. RESULTS: Patient characteristics reflected stable, chronic HF with reduced ejection fraction with high use of optimal medical therapy. There was no significant difference in average 6- and 12-week adjusted NT-proBNP with dapagliflozin versus placebo (1133 pg/dL (95% CI 1036-1238) vs 1191 pg/dL (95% CI 1089-1304), P=0.43). For the second dual-primary outcome of a meaningful improvement in Kansas City Cardiomyopathy Questionnaire overall summary score or NT-proBNP, 61.5% of dapagliflozin-treated patients met this end point versus 50.4% with placebo (adjusted OR 1.8, 95% CI 1.03-3.06, nominal P=0.039). This was attributable to both higher proportions of patients with ≥5-point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score (42.9 vs 32.5%, adjusted OR 1.73, 95% CI 0.98-3.05), and ≥20% reduction in NT-proBNP (44.0 vs 29.4%, adjusted OR 1.9, 95% CI 1.1-3.3) by 12 weeks. Results were consistent among patients with or without type 2 diabetes mellitus, and other prespecified subgroups (all P values for interaction=NS). CONCLUSIONS: In patients with heart failure and reduced ejection fraction, use of dapagliflozin over 12 weeks did not affect mean NT-proBNP but increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. Benefits of dapagliflozin on clinically meaningful HF measures appear to extend to patients without type 2 diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02653482.

2.
J Phys Chem Lett ; 8(6): 1175-1178, 2017 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-28234013

RESUMO

Materials that luminesce after excitation with ionizing radiation are extensively applied in physics, medicine, security, and industry. Lanthanide dopants are known to trigger crystal scintillation through their fast d-f emissions; the same is true for other important applications as lasers or phosphors for lighting. However, this ability can be seriously compromised by unwanted anomalous emissions often found with the most common lanthanide activators. We report high-resolution X-ray-excited optical (IR to UV) luminescence spectra of CaF2:Yb and SrF2:Yb samples excited at 8949 eV and 80 K. Ionizing radiation excites the known anomalous emission of ytterbium in the CaF2 host but not in the SrF2 host. Wave function-based ab initio calculations of host-to-dopant electron transfer and Yb2+/Yb3+ intervalence charge transfer explain the difference. The model also explains the lack of anomalous emission in Yb-doped SrF2 excited by VUV radiation.

3.
Transpl Infect Dis ; 19(1)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27943503

RESUMO

BACKGROUND: Invasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution. METHODS: A prospective cohort study of 159 heart transplant recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: By univariate analysis, Hispanic ethnicity was associated with IFI (P=.01, odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-27.9). Subsequently, a multivariate logistic regression was performed adjusting for Hispanic ethnicity, age, and gender. Seventeen IFIs were identified, occurring at a median 110 days post HT (interquartile range: 32-411 days). Five IFIs (29% of IFIs and 3.1% of all HT) occurred during the HT hospitalization, with 13 IFIs during the first year (incidence 8.2%). CONCLUSIONS: The cumulative incidence was 10.7%. IFIs were associated with pre- and post-HT vancomycin-resistant Enterococcus colonization and/or infection, post-HT renal replacement therapy, anti-thymocyte globulin induction, and antibody-mediated rejection. There were no associations with diabetes mellitus, desensitization, 2R/3R cellular rejection, treatments for rejection, re-operation, neutropenia, or cytomegalovirus infection. IFIs were associated with death (P=.02, OR 3.9, 95% CI 1.3-12.1) and 1-year mortality (P<.001, OR 9.0, 95% CI 2.3-35.7), but not 3-year mortality. Associations with Hispanic ethnicity must be validated. Optimal strategies for risk reduction and prophylaxis remain undefined.


Assuntos
Soro Antilinfocitário/efeitos adversos , Rejeição de Enxerto/complicações , Infecções por Bactérias Gram-Positivas/complicações , Transplante de Coração/efeitos adversos , Imunossupressores/efeitos adversos , Infecções Fúngicas Invasivas/complicações , Infecções Fúngicas Invasivas/epidemiologia , Enterococos Resistentes à Vancomicina/isolamento & purificação , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/uso terapêutico , Feminino , Rejeição de Enxerto/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Diálise Renal/efeitos adversos , Fatores de Risco
4.
J Hazard Mater ; 325: 120-128, 2017 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-27930996

RESUMO

Mercury (Hg) is widely distributed in different localities around the world and poses a serious health threat to humans, especially when ingested in the form of methylmercury (MeHg). Efforts have been directed toward decreasing the production of MeHg by converting Hg to stable forms. Activated carbon and biochar have been evaluated as stabilization agents for Hg in contaminated sediments. However, the long-term fate of Hg stabilized by these materials remains unclear. Here, we compare the effectiveness of Hg stabilization using two biochars prepared from switchgrass at 300°C (lowT) and 600°C (highT). Experiments were conducted by co-blending biochars and sediment for >600 d under anaerobic conditions. Aqueous concentrations of total Hg and MeHg were greatly reduced in the presence of biochars, with the exception of a spike in MeHg concentration observed at ∼440 d in the high-T biochar system. Hg co-occurs with S, Fe, Cu, and other elements within the plant structure of low-T biochar particles, but primarily on the outer surfaces of high-T biochar particles. Our results indicate that the stabilization of Hg may be through an early-stage diagenetic process, suggesting that the stabilization of Hg by biochar may be effective over long time frames.


Assuntos
Carvão Vegetal/química , Sedimentos Geológicos/química , Mercúrio/química , Compostos de Metilmercúrio/química , Poluentes Químicos da Água/química , Carbono/análise , Cobre/análise , Ferro/análise , Mercúrio/análise , Metilação , Compostos de Metilmercúrio/análise , Panicum , Rios , Enxofre/análise , Poluentes Químicos da Água/análise
5.
J Phys Condens Matter ; 28(13): 135502, 2016 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-26941175

RESUMO

Ytterbium-doped wide-bandgap fluoride crystals CaF2, SrF2 and NaMgF3 have been measured using x-ray absorption near edge structure (XANES) on the L3 edge to determine the ratio of trivalent to divalent Yb ions present in the crystals. This study improves upon previous XANES measurements of dopant ion valency by taking into account the x-ray emission transition probabilities for the divalent and trivalent species instead of simply assuming that the relative concentrations may be determined by the ratio of the x-ray excitation band areas. Trivalent to divalent ratios as high as 5 are inferred even at low total dopant ion concentrations of 0.05 mol% Yb.

6.
J Phys Condens Matter ; 27(33): 335501, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26221981

RESUMO

We present an investigation of the valence-electron excitation spectra including the collective plasmon modes of SrTiO3, LaAlO3 and their heterostructures with non-resonant inelastic x-ray scattering. We analyse the spectra using calculations based on first principles and atomic multiplet models. We demonstrate the feasibility of performing valence IXS experiments in a total reflection geometry. Surprisingly, we find that the plasmon, interband and semicore excitations in multilayers are well described as a superposition of bulk-compound spectra even in a superstructure composing of layers of only one atomic layer thickness.

7.
Environ Sci Technol ; 49(4): 2255-61, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25607235

RESUMO

Maternal transfer of elevated selenium (Se) to offspring is an important route of Se exposure for fish in the natural environment. However, there is a lack of information on the tissue specific spatial distribution and speciation of Se in the early developmental stages of fish, which provide important information about Se toxicokinetics. The effect of maternal transfer of Se was studied by feeding adult zebrafish a Se-elevated or a control diet followed by collection of larvae from both groups. Novel confocal synchrotron-based techniques were used to investigate Se within intact preserved larvae. Confocal X-ray fluorescence imaging was used to compare Se distributions within specific planes of an intact larva from each of the two groups. The elevated Se treatment showed substantially higher Se levels than the control; Se preferentially accumulated to highest levels in the eye lens, with lower levels in the retina, yolk and other tissues. Confocal X-ray absorption spectroscopy was used to determine that the speciation of Se within the eye lens of the intact larva was a selenomethionine-like species. Preferential accumulation of Se in the eye lens may suggest a direct cause-and-effect relationship between exposure to elevated Se and Se-induced ocular impairments reported previously. This study illustrates the effectiveness of confocal X-ray fluorescence methods for investigating trace element distribution and speciation in intact biological specimens.


Assuntos
Cristalino/metabolismo , Selênio/farmacocinética , Poluentes Químicos da Água/farmacocinética , Animais , Feminino , Larva , Exposição Materna , Imagem Óptica , Espectroscopia por Absorção de Raios X , Peixe-Zebra
8.
Congest Heart Fail ; 19(2): 53-60, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23336425

RESUMO

Despite the widespread use of loop diuretics to treat acute decompensated heart failure (ADHF), robust data supporting their role and optimal dosing strategies are scarce. This analysis aimed to compare clinical outcomes of patients admitted with ADHF who received a diuretic dosing protocol with those who received the usual diuretic therapy. We performed an observational medical records review to compare the use of a nurse-driven diuretic dosing protocol with usual diuretic dosing for patients admitted with ADHF during a 1-year period. Using a propensity scoring model, comparisons were made between groups for total weight loss, length of stay (LOS), 30-day readmissions, in-hospital mortality, 30-day mortality, and acute kidney failure. Sixty-eight of the 596 patients admitted with ADHF during the study period received the diuretic protocol. Protocol use was associated with an additional 2.63-kg weight loss (P=.003) but a trend toward increased LOS compared with patients receiving usual care (P=.097). However, patients receiving the protocol had a significantly lower risk of 30-day readmission (odds ratio, 0.46, 95% confidence interval, 0.22-0.95). Protocol use was not associated with significant differences in kidney failure, inpatient mortality, or 30-day mortality. A diuretic dosing protocol for patients admitted with ADHF improves weight loss and may lower 30-day readmissions, at the cost of potentially increasing LOS.


Assuntos
Volume Sanguíneo/efeitos dos fármacos , Bumetanida/administração & dosagem , Furosemida/administração & dosagem , Insuficiência Cardíaca , Doença Aguda , Administração Intravenosa , Idoso , Distribuição de Qui-Quadrado , Protocolos Clínicos , Diuréticos/administração & dosagem , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
J Chem Phys ; 136(19): 194501, 2012 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-22612097

RESUMO

We report a resonant inelastic x-ray scattering (RIXS) study of crystalline CeB(6). Ce L(α1,2) RIXS was measured with excitation energies resonant with the Ce L(3)-edge. A lifetime-broadening suppressed x-ray absorption near-edge structure (LBS-XANES), which successfully reproduced the L(α1,2) RIXS spectra over wide ranges of excitation and emission energies, was simulated using the SIM-RIXS program. A pre-edge structure in the LBS-XANES can be resolved, and many-body effects were suggested in the L(α1,2) RIXS around the Ce L(3)-edge energy. No convincing signs of Ce (II) or Ce (IV) states were observed in the LBS-XANES. Ce L(γ4) RIXS was measured at 302 K and 28 K with excitation energies across the Ce L(1)-edge. The interactions of p-valence electrons between Ce and B(6) were found to be considerably small, regardless of temperature. Thus, the electronic state of CeB(6) was concluded to be suitably described as a nominally Ce(4f(1))(3+)(e(-))(B(6))(2-) system with some hybridization among all valence orbitals of Ce and B.

10.
J AAPOS ; 13(6): 602-4, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20006827

RESUMO

A 15-year-old girl being treated with imatinib for chronic myelogenous leukemia (CML) presented with acute vision loss in her right eye accompanied by swelling of the right side of her neck. On examination, she was found to have disk and macular edema of the right eye. Fine-needle aspiration and excisional biopsies of an enlarged submandibular lymph node were negative for malignancy. Although initial serologies were equivocal for Bartonella henselae, repeat serologies performed 1 week later upon the appearance of a macular star were positive. This is the first reported case of B. henselae in a patient with CML.


Assuntos
Bartonella henselae/isolamento & purificação , Doença da Arranhadura de Gato/microbiologia , Infecções Oculares Bacterianas , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Retinite/microbiologia , Adolescente , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/sangue , Antineoplásicos/uso terapêutico , Bartonella henselae/imunologia , Benzamidas , Doença da Arranhadura de Gato/diagnóstico , Doença da Arranhadura de Gato/tratamento farmacológico , Doxiciclina/uso terapêutico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Feminino , Angiofluoresceinografia , Humanos , Mesilato de Imatinib , Imunoglobulina G/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Edema Macular/microbiologia , Imagem por Ressonância Magnética , Papiledema/microbiologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Retinite/diagnóstico , Retinite/tratamento farmacológico , Tomografia de Coerência Óptica
11.
Environ Sci Technol ; 43(13): 4818-23, 2009 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19673270

RESUMO

The distribution and chemical form (speciation) of arsenic in terrestrial food chains determines both the amount of arsenic available to higher organisms, and the toxicity of this metalloid in affected ecosystems. Invertebrates are part of complex terrestrial food webs. This paper provides arsenic concentrations and arsenic speciation profiles for eight orders of terrestrial invertebrates collected at three historical gold mine sites and one background site in Nova Scotia, Canada. Total arsenic concentrations, determined by inductively coupled plasma mass spectrometry (ICP-MS), were dependent upon the classification of invertebrate. Arsenic species were determined by high-performance liquid chromatography (HPLC) ICP-MS and X-ray absorption spectroscopy (XAS). Invertebrates were found by HPLC ICP-MS to contain predominantly arsenite and arsenate in methanol/water extracts, while XAS revealed that most arsenic is bound to sulfur in vivo. Examination of the spatial distribution of arsenic within an ant tissue highlighted the differences between exogenous and endogenous arsenic, as well as the extent to which arsenic is transformed upon ingestion. Similar arsenic speciation patterns for invertebrate groups were observed across sites. Trace amounts of arsenobetaine and arsenocholine were identified in slugs, ants, and spiders.


Assuntos
Arsênico/toxicidade , Animais , Formigas/efeitos dos fármacos , Arseniatos/química , Arsenitos/química , Cromatografia Líquida de Alta Pressão/métodos , Cadeia Alimentar , Gastrópodes/efeitos dos fármacos , Invertebrados/efeitos dos fármacos , Espectrometria de Massas/métodos , Metanol/química , Poluentes do Solo/análise , Especificidade da Espécie , Espectrometria por Raios X/métodos , Aranhas/efeitos dos fármacos , Água/química
13.
Environ Sci Technol ; 40(20): 6304-9, 2006 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17120557

RESUMO

The mechanisms of gold bioaccumulation by cyanobacteria (Plectonema boryanum UTEX 485) from gold(III)-chloride solutions have been studied at three gold concentrations (0.8,1.7, and 7.6 mM) at 25 degrees C, using both fixed-time laboratory and real-time synchrotron radiation absorption spectroscopy (XAS) experiments. Interaction of cyanobacteria with aqueous gold(III)-chloride initially promoted the precipitation of nanoparticles of amorphous gold(I)-sulfide at the cell walls, and finally deposited metallic gold in the form of octahedral (111) platelets (approximately 10 nm to 6 microm) near cell surfaces and in solutions. The XAS results confirm that the reduction mechanism of gold(III)-chloride to metallic gold by cyanobacteria involves the formation of an intermediate Au(I) species, gold(I)-sulfide.


Assuntos
Cianobactérias/metabolismo , Compostos de Ouro/metabolismo , Ouro/metabolismo , Cianobactérias/ultraestrutura , Ouro/química , Compostos de Ouro/química , Microscopia Eletrônica de Transmissão/métodos , Nanoestruturas/ultraestrutura , Fatores de Tempo
14.
Arch Ophthalmol ; 124(6): 766-73, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16769828

RESUMO

OBJECTIVE: To present strabismus data for premature infants with prethreshold retinopathy of prematurity (ROP) enrolled in the Early Treatment for Retinopathy of Prematurity study. DESIGN: The prevalence of strabismus was tabulated for all of the infants with high-risk prethreshold disease who participated in the randomized trial of the Early Treatment for Retinopathy of Prematurity study and were examined at 6 and/or 9 months' corrected age as well as for all of the infants with low-risk prethreshold disease who were examined at 6 months' corrected age. MAIN OUTCOME MEASURES: Presence or absence of strabismus at 6 and 9 months' corrected age. RESULTS: The prevalence of strabismus at 6 months was higher for infants with high-risk prethreshold ROP than for those with low-risk prethreshold ROP (20.3% vs 9.6%, respectively; P<.001). Risk factors associated with the development of strabismus at 9 months include abnormal fixation behavior, presence of amblyopia, and outborn birth status (ie, born outside of a study-affiliated hospital). At 9 months, 30% of infants with high-risk prethreshold ROP had strabismus, although only 42% showed strabismus at 6 months. Thirty percent of infants with strabismus at 6 months showed normal alignment at 9 months. CONCLUSIONS: Infants with high-risk prethreshold ROP show significant variability in the presence vs absence of strabismus in the first year of life; thus, conservative management is recommended. APPLICATION TO CLINICAL PRACTICE: Ophthalmologists managing strabismus in infants who have high-risk prethreshold ROP should be aware of the significant variability in ocular alignment during the first year of life.


Assuntos
Retinopatia da Prematuridade/complicações , Estrabismo/epidemiologia , Estrabismo/fisiopatologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Fotocoagulação a Laser , Masculino , Prevalência , Estudos Prospectivos , Retinopatia da Prematuridade/fisiopatologia , Retinopatia da Prematuridade/cirurgia , Fatores de Risco , Acuidade Visual
15.
Environ Sci Technol ; 39(1): 248-54, 2005 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-15667101

RESUMO

Arsenic is an element that is ubiquitous in the environment and is known to form compounds with toxic, even carcinogenic properties. Arsenic toxicity is a function of its chemical form (species). Identification of arsenic species is necessary to accurately determine the transformation and fate of arsenicals as well as the actual risk posed by arsenic contamination. We report X-ray absorption near-edge structure (XANES) measurements of 16 biologically important arsenic compounds. Solid and aqueous standards were studied for differences in XANES spectral features, white line positions, stability during exposure to the beam, and stability between two beam exposures separated by 48 h. Samples containing As(III) (11870.0-11871.7+/-0.5 eV) and As(V) (11872.6-11875.3+/-0.5 eV) were easily distinguished by white line energies and could be further subdivided into a total of seven groups. Valuable examples include As(III)-sulfur compounds (11870.0+/-0.5 eV), arsenobetaine and arsenocholine (11872.6+/-0.5 eV), and a dimethyl arsinyl riboside (11873.3+/-0.5 eV). A growing number of environmental and biological studies use X-ray absorption spectroscopy (XAS) results to complement their more traditional analyses. Results provided here are intended to help make XAS more accessible to new users interested in the study of arsenic in the environment.


Assuntos
Arsênico/análise , Arsênico/química , Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Disponibilidade Biológica , Análise Espectral/métodos
16.
J AAPOS ; 8(6): 588-91, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15616510

RESUMO

Russell-Silver syndrome (RSS) primarily includes intrauterine growth retardation, postnatal growth failure, body asymmetry, and craniofacial disproportion. Four types of malignancies have been reported in patients with RSS: craniopharyngioma, testicular seminoma, hepatocellular carcinoma, and Wilms tumor.


Assuntos
Retardo do Crescimento Fetal/complicações , Doenças Orbitárias/complicações , Pseudolinfoma/complicações , Pré-Escolar , Feminino , Retardo do Crescimento Fetal/diagnóstico , Idade Gestacional , Humanos , Imagem por Ressonância Magnética , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/cirurgia , Pseudolinfoma/diagnóstico , Pseudolinfoma/cirurgia , Síndrome
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