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1.
Molecules ; 24(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739621

RESUMO

Hyperpolarization methods, which increase the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), have the potential to expand the range of applications of these powerful analytical techniques and to enable the use of smaller and cheaper devices. The signal amplification by reversible exchange (SABRE) method is of particular interest because it is relatively low-cost, straight-forward to implement, produces high-levels of renewable signal enhancement, and can be interfaced with low-cost and portable NMR detectors. In this work, we demonstrate an in situ approach to SABRE hyperpolarization that can be achieved using a simple, commercially-available Earth's field NMR detector to provide 1H polarization levels of up to 3.3%. This corresponds to a signal enhancement over the Earth's magnetic field by a factor of ε > 2 × 108. The key benefit of our approach is that it can be used to directly probe the polarization transfer process at the heart of the SABRE technique. In particular, we demonstrate the use of in situ hyperpolarization to observe the activation of the SABRE catalyst, the build-up of signal in the polarization transfer field (PTF), the dependence of the hyperpolarization level on the strength of the PTF, and the rate of decay of the hyperpolarization in the ultra-low-field regime.


Assuntos
Campos Magnéticos , Espectroscopia de Ressonância Magnética/métodos , Catálise
2.
J Trauma Acute Care Surg ; 85(3): 476-484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29787535

RESUMO

BACKGROUND: Fatigued surgeon performance has only been assessed in simulated sessions or retrospectively after a night on call. We hypothesized that objectively assessed fatigue of acute care surgeons affects patient outcome. METHODS: Five acute care surgery services prospectively identified emergency cases over 27 months. Emergency cases were defined by the surgeon identifying the patient as requiring immediate operation upon consultation or admission. Within 48 hours, surgeons reported sleep time accumulated before operation, if nonclinical delays to operation occurred, and patient volume during the shift. To maximize differences, fatigued surgeons were defined as performing a case after midnight without having slept in the prior 18 hours. Rested surgeons performed cases at or before 8 PM or after at least 3 hours of sleep before operation. A four-level ordinal scale was used to assign case complexity. Hierarchical logistic regression models were constructed to assess the impact of fatigue on mortality and major morbidity while controlling for center and patient level factors. RESULTS: Of 882 cases collected, 611 met criteria for fatigue or rested. Of these cases, 370 were performed at night and 182 by a fatigued surgeon. Rested surgeons were more likely to be operating on an older or female patient; other characteristics were similar. Mortality and major morbidity were similar between fatigued and rested surgeons (12.1% vs 12.1% and 46.9% vs 48.9%), respectively. After controlling for center and patient factors, surgeon fatigue did not affect mortality or major morbidity. Mortality variance was 6.30% and morbidity variance was 7.02% among centers. CONCLUSION: Acute care surgeons have similar outcomes in a fatigued or rested state. Work schedules for acute care surgeons should not be adjusted to shifts less than 24 hours for the sole purpose of improving patient outcomes. LEVEL OF EVIDENCE: Prognostic study, level IV.


Assuntos
Fadiga/complicações , Cirurgiões/estatística & dados numéricos , Desempenho Profissional/estatística & dados numéricos , Adulto , Idoso , Competência Clínica/estatística & dados numéricos , Cuidados Críticos/estatística & dados numéricos , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Admissão e Escalonamento de Pessoal/tendências , Estudos Prospectivos , Fatores de Risco , Cirurgiões/psicologia
3.
PLoS Negl Trop Dis ; 12(1): e0006186, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29364883

RESUMO

The mosquito Aedes aegypti is the primary vector of human arboviral diseases caused by dengue, chikungunya and Zika viruses. Many studies have shown the potential roles of small RNA molecules such as microRNA, small interfering RNA and PIWI-interacting RNA in vector mosquitoes. The function of tRNA fragments (tRF), the newly discovered class of small RNAs, in mosquitoes is not known. In this study, we show that specific tRFs are expressed in significantly differential manner between males and females of Ae. aegypti strains. Specific tRFs also show differential response during developmental transition from larvae to adults, as well as after blood feeding of adult females. The expression pattern of tRFs upon blood feeding varied depending upon if the blood contained dengue virus, and also if the females were treated with antibiotic prior to feeding to cleanse of the gut bacteria. Our findings show that a single tRF derived from the precursor sequences of a tRNA-Gly was differentially expressed between males and females, developmental transitions and also upon blood feeding by females of two laboratory strains that vary in midgut susceptibility to dengue virus infection. The multifaceted functional implications of this specific tRF suggest that biogenesis of small regulatory molecules from a tRNA can have wide ranging effects on key aspects of Ae. aegypti vector biology.


Assuntos
Aedes/genética , Regulação da Expressão Gênica no Desenvolvimento , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Aedes/crescimento & desenvolvimento , Animais , Feminino , Perfilação da Expressão Gênica , Larva/genética , Larva/crescimento & desenvolvimento , Masculino
4.
PLoS One ; 11(7): e0158706, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27437989

RESUMO

The development of new biological and chemical instruments for research and diagnostic applications is often slowed by the cost, specialization, and custom nature of these instruments. New instruments are built from components that are drawn from a host of different disciplines and not designed to integrate together, and once built, an instrument typically performs a limited number of tasks and cannot be easily adapted for new applications. Consequently, the process of inventing new instruments is very inefficient, especially for researchers or clinicians in resource-limited settings. To improve this situation, we propose that a family of standardized multidisciplinary components is needed, a set of "building blocks" that perform a wide array of different tasks and are designed to integrate together. Using these components, scientists, engineers, and clinicians would be able to build custom instruments for their own unique needs quickly and easily. In this work we present the foundation of this set of components, a system we call Multifluidic Evolutionary Components (MECs). "Multifluidic" conveys the wide range of fluid volumes MECs operate upon (from nanoliters to milliliters and beyond); "multi" also reflects the multiple disciplines supported by the system (not only fluidics but also electronics, optics, and mechanics). "Evolutionary" refers to the design principles that enable the library of MEC parts to easily grow and adapt to new applications. Each MEC "building block" performs a fundamental function that is commonly found in biological or chemical instruments, functions like valving, pumping, mixing, controlling, and sensing. Each MEC also has a unique symbol linked to a physical definition, which enables instruments to be designed rapidly and efficiently using schematics. As a proof-of-concept, we use MECs to build a variety of instruments, including a fluidic routing and mixing system capable of manipulating fluid volumes over five orders of magnitude, an acid-base titration instrument suitable for use in schools, and a bioreactor suitable for maintaining and analyzing cell cultures in research and diagnostic applications. These are the first of many instruments that can be built by researchers, clinicians, and students using the MEC system.


Assuntos
Desenho de Equipamento/métodos , Dispositivos Lab-On-A-Chip , Óptica e Fotônica/instrumentação , Humanos
5.
Proc Natl Acad Sci U S A ; 113(12): 3164-8, 2016 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-26961001

RESUMO

Hyperpolarized (hp) (83)Kr is a promising MRI contrast agent for the diagnosis of pulmonary diseases affecting the surface of the respiratory zone. However, the distinct physical properties of (83)Kr that enable unique MRI contrast also complicate the production of hp (83)Kr. This work presents a previously unexplored approach in the generation of hp (83)Kr that can likewise be used for the production of hp (129)Xe. Molecular nitrogen, typically used as buffer gas in spin-exchange optical pumping (SEOP), was replaced by molecular hydrogen without penalty for the achievable hyperpolarization. In this particular study, the highest obtained nuclear spin polarizations were P =29% for(83)Kr and P= 63% for (129)Xe. The results were reproduced over many SEOP cycles despite the laser-induced on-resonance formation of rubidium hydride (RbH). Following SEOP, the H2 was reactively removed via catalytic combustion without measurable losses in hyperpolarized spin state of either (83)Kr or (129)Xe. Highly spin-polarized (83)Kr can now be purified for the first time, to our knowledge, to provide high signal intensity for the advancement of in vivo hp (83)Kr MRI. More generally, a chemical reaction appears as a viable alternative to the cryogenic separation process, the primary purification method of hp(129)Xe for the past 2 1/2 decades. The inherent simplicity of the combustion process will facilitate hp (129)Xe production and should allow for on-demand continuous flow of purified and highly spin-polarized (129)Xe.


Assuntos
Meios de Contraste , Hidrogênio/química , Criptônio/química , Xenônio/química , Catálise , Imageamento por Ressonância Magnética
6.
Acta Trop ; 140: 151-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25193134

RESUMO

Significant morbidity and potential mortality following dengue virus infection is a re-emerging global health problem. Due to the limited effectiveness of current disease control methods, mosquito biologists have been searching for new methods of controlling dengue transmission. While much effort has concentrated on determining genetic aspects to vector competence, paratransgenetic approaches could also uncover novel vector control strategies. The interactions of mosquito midgut microflora and pathogens may play significant roles in vector biology. However, little work has been done to see how the microbiome influences the host's fitness and ultimately vector competence. Here we investigated the effects of the midgut microbial environment and dengue infection on several fitness characteristics among three strains of the primary dengue virus vector mosquito Aedes aegypti. This included comparisons of dengue infection rates of females with and without their normal midgut flora. According to our findings, few effects on fitness characteristics were evident following microbial clearance or with dengue virus infection. Adult survivorship significantly varied due to strain and in one strain varied due to antibiotic treatment. Fecundity varied in one strain due to microbial clearance by antibiotics but no variation was observed in fertility due to either treatment. We show here that fitness characteristics of Ae. aegypti vary largely between strains, including varying response to microflora presence or absence, but did not vary in response to dengue virus infection.


Assuntos
Aedes/virologia , Vírus da Dengue/crescimento & desenvolvimento , Dengue/transmissão , Insetos Vetores/virologia , Aedes/microbiologia , Animais , Vírus da Dengue/isolamento & purificação , Feminino , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/virologia , Insetos Vetores/microbiologia , Controle de Mosquitos , Ovinos
7.
Artigo em Inglês | MEDLINE | ID: mdl-25570076

RESUMO

Microfluidic diagnostics for use in the developing world face a number of unique challenges. Doctors and nurses in developing countries are best suited to addresses these challenges, but they lack the resources and training needed to develop their own microfluidic diagnostics. To address this need, we are developing a system of Multifluidic Evolutionary Components or MECs, "building blocks" that can be snapped together by healthcare providers in resource-limited settings to build custom diagnostic instruments. MECs operate on multiple scales of fluid volumes (from nanoliters to milliliters) and include not only fluidic but also optical, mechanical, and electronic functions. In this work we share several prototype MECs and use them to build a demonstration instrument capable of measuring the pH of a sample.


Assuntos
Técnicas Analíticas Microfluídicas/instrumentação , Doenças Transmissíveis/diagnóstico , Países em Desenvolvimento , Humanos , Malária/diagnóstico , Técnicas Analíticas Microfluídicas/métodos , Tuberculose/diagnóstico
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