Dissolution DNP-NMR spectroscopy using galvinoxyl as a polarizing agent.

The goal of this work was to test feasibility of using galvinoxyl (2,6-di-tert-butyl-α-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p-tolyloxy) as a polarizing agent for dissolution dynamic nuclear polarization (DNP) NMR spectroscopy. We have found that galvinoxyl is reasonably soluble in ethyl acetate, chloroform, or acetone and the solutions formed good glasses when mixed together or with other solvents such as dimethyl sulfoxide. W-band electron spin resonance (ESR) measurements revealed that galvinoxyl has an ESR linewidth D intermediate between that of carbon-centered free radical trityl OX063 and the nitroxide-based 4-oxo-TEMPO, thus the DNP with galvinoxyl for nuclei with low gyromagnetic ratio γ such as (13)C and (15)N is expected to proceed predominantly via the thermal mixing process.

The efficiency of DPPH as a polarising agent for DNP-NMR spectroscopy.

The free radical 2,2-diphenyl-1-pycrylhydrazyl (DPPH) was tested as a polarising agent for fast dissolution dynamic nuclear polarisation (DNP) NMR spectroscopy. DPPH was found to be reasonably soluble in sulfolane and the optimum concentration for DNP is 20-40 mM depending upon whether short polarisation times or the maximum signal intensity is needed. W-band ESR measurements revealed that the ESR linewidth D of DPPH is intermediate between that of BDPA and 4-oxo-TEMPO.

Responsibilities to plan for ancillary care pose ethical challenges for nutrition research in the community setting.

Investigators who conduct nutrition research in the community setting, particularly among underserved populations, face the ethical question of whether and how to respond to participants' unmet health needs. The research ethics literature conceptualizes this question as one of ancillary care (AC): what is the nature and extent of researchers' ethical responsibilities, if any, to provide or facilitate health care that research participants need but that is not necessary to ensure the safety or scientific validity of the research? In this paper, we highlight 3 ethical challenges involved in the planning of AC responses for nutrition research conducted in the community setting: influence of provision of AC on primary study outcomes as an issue of trial design; whether to extend the provision of AC beyond research participants to nonparticipants with the same health needs; and how best to train field workers who may be the most likely members of the study team to encounter the health needs anticipated among participants. Although the global ethical discussion of AC is gaining in depth, breadth, and practical influence, it remains relatively uninformed by perspectives specific to nutrition research.

The ethics of testing a test: randomized trials of the health impact of diagnostic tests for infectious diseases.

In the last decade, many new rapid diagnostic tests for infectious diseases have been developed. In general, these new tests are developed with the intent to optimize feasibility and population health, not accuracy alone. However, unlike drugs or vaccines, diagnostic tests are evaluated and licensed on the basis of accuracy, not health impact (eg, reduced morbidity or mortality).

Duarte galactose-1-phosphate uridyl transferase genotypes are not associated with ovarian cancer risk.

Objective: To investigate whether galactose-1-phosphate uridyl transferase (GALT) variant genotypes were associated with epithelial ovarian cancer risk, and to determine if this association was modified by lactose intake.

Design: Two prospective cohort studies and a case-control study.

Setting: Academic institution.

Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes.

Inconsistent results for the role of dairy food intake in relation to ovarian cancer risk may reflect the potential adverse effects of lactose, which has been hypothesized to increase gonadotropin levels, and the beneficial antiproliferative effects of calcium and vitamin D. Using data from the New England case-control study (1,909 cases and 1,989 controls), we examined dairy foods and nutrients in relation to risk of ovarian cancer overall, histological subtypes and rapidly fatal versus less aggressive disease. We used logistic regression and polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Short-time windows of correlation between large-scale functional brain networks predict vigilance intraindividually and interindividually.

A better understanding of how behavioral performance emerges from interacting brain systems may come from analysis of functional networks using functional magnetic resonance imaging. Recent studies comparing such networks with human behavior have begun to identify these relationships, but few have used a time scale small enough to relate their findings to variation within a single individual's behavior. In the present experiment we examined the relationship between a psychomotor vigilance task and the interacting default mode and task positive networks.

Provision of community-wide benefits in public health intervention research: the experience of investigators conducting research in the community setting in South Asia.

Background: This article describes the types of community-wide benefits provided by investigators conducting public health research in South Asia as well as their self-reported reasons for providing such benefits.

Methods: We conducted 52 in-depth interviews to explore how public health investigators in low-resource settings make decisions about the delivery of ancillary care to research subjects. In 39 of the interviews respondents described providing benefits to members of the community in which they conducted their study.

Impact of Gd3+ on DNP of [1-13C]pyruvate doped with trityl OX063, BDPA, or 4-oxo-TEMPO.

Hyperpolarized [1-(13)C]pyruvate has become an important diagnostic tracer of normal and aberrant cellular metabolism for in vitro and in vivo NMR spectroscopy (MRS) and imaging (MRI). In pursuit of achieving high NMR signal enhancements in dynamic nuclear polarization (DNP) experiments, we have performed an extensive investigation of the influence of Gd(3+) doping, a parameter previously reported to improve hyperpolarized NMR signals, on the DNP of this compound. [1-(13)C]Pyruvate samples were doped with varying amounts of Gd(3+) and fixed optimal concentrations of free radical polarizing agents commonly used in fast dissolution DNP: trityl OX063 (15 mM), 4-oxo-TEMPO (40 mM), and BDPA (40 mM).

Increased risk of neoplasm in appendicitis treated with interval appendectomy: single-institution experience and literature review.

Appendicitis is a common diagnosis encountered by the acute care surgeon. Management of complicated appendicitis is controversial and often involves initial nonoperative therapy with interval appendectomy. This study reviews single-institutional experience with management of complicated appendicitis with interval appendectomy and addresses an unusually high occurrence of incidental appendiceal malignancies observed with a review of relevant literature.

Comparison of kinetic models for analysis of pyruvate-to-lactate exchange by hyperpolarized 13 C NMR.

The activity of specific enzyme-catalyzed reactions may be detected in vivo by (13) C NMR of hyperpolarized (HP) substrates. The signals from HP substrates and products, acquired over time, have been fitted to a number of different mathematical models to determine fluxes, but these models have not been critically compared. In this study, two-pool and three-pool first-order models were constructed to measure flux through lactate dehydrogenase in isolated glioblastoma cells by NMR detection of lactate and pyruvate following the addition of HP [1-(13) C]pyruvate.

Nanoparticle-based PARACEST agents: the quenching effect of silica nanoparticles on the CEST signal from surface-conjugated chelates.

Silica nanoparticles of average diameter 53 ± 3 nm were prepared using standard water-in-oil microemulsion methods. After conversion of the surface Si-OH groups to amino groups for further conjugation, the PARACEST agent, EuDOTA-(gly)₄ (-) was coupled to the amines via one or more side-chain carboxyl groups in an attempt to trap water molecules in the inner-sphere of the complex. Fluorescence and ICP analyses showed that approximately 1200 Eu(3+) complexes were attached to each silica nanoparticle, leaving behind excess protonated amino groups.

Laparoscopic management of acute small bowel obstruction: evaluating the need for resection.

Background: Acute small bowel obstruction (SBO) is a common condition encountered by the on-call emergency surgeon. The role of laparoscopy in the management of SBO continues to be defined. This modality can be limited by dilated bowel and inadequate assessment of compromised tissue.

Ovarian cancer spheroids use myosin-generated force to clear the mesothelium.

Dissemination of ovarian tumors involves the implantation of cancer spheroids into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. Biopsies of tumors attached to peritoneal organs show that mesothelial cells are not present under tumor masses. We have developed a live, image-based in vitro model in which interactions between tumor spheroids and mesothelial cells can be monitored in real time to provide spatial and temporal understanding of mesothelial clearance.

Health researchers' ancillary care obligations in low-resource settings: how can we tell what is morally required?

Health researchers working in low-resource settings often encounter serious unmet health needs among participants. What is the nature and extent of researchers' obligations to respond to such needs? Competing accounts have been proposed, but there is no independent standard by which to assess them or to guide future inquiry. I propose an independent standard and demonstrate its use.

Molecular pathogenesis of endometrial and ovarian cancer.

Pregnancy, breastfeeding, and oral contraceptive pill use interrupt menstrual cycles and reduce endometrial and ovarian cancer risk. This suggests the importance of turnover within Mullerian tissues, where the accumulation of mutations in p53 and PTEN has been correlated with number of cycles. The most common type of endometrial cancer (Type I) is endometrioid and molecular abnormalities include mutations in PTEN, KRAS and β-catenin.

Flux through hepatic pyruvate carboxylase and phosphoenolpyruvate carboxykinase detected by hyperpolarized 13C magnetic resonance.

In the heart, detection of hyperpolarized [(13)C]bicarbonate and (13)CO(2) by magnetic resonance (MR) after administration of hyperpolarized [1-(13)C]pyruvate is caused exclusively by oxidative decarboxylation of pyruvate via the pyruvate dehydrogenase complex (PDH). However, liver mitochondria possess alternative anabolic pathways accessible by [1-(13)C]pyruvate, which may allow a wider diagnostic range for hyperpolarized MR compared with other tissue. Metabolism of hyperpolarized [1-(13)C]pyruvate in the tricarboxylic acid (TCA) cycle was monitored in the isolated perfused liver from fed and fasted mice.

Cardiovascular-emotional dampening: the relationship between blood pressure and recognition of emotion.

Objective: Persons with elevated blood pressure (BP) show dampened emotional responses to affect-laden stimuli. We sought to further examine cardiovascular-emotional dampening by examination of the relationship between resting hemodynamic measures and recognition of emotion in an African American community-based sample.

Methods: Participants were 106 African American men and women (55 women; mean age = 52.

Differences in regional myocardial perfusion, metabolism, MVO2, and edema after coronary sinus machine perfusion preservation of canine hearts.

Machine perfusion improves solid organ preservation for transplantation. We have demonstrated that antegrade perfusion preservation of hearts is superior to cold storage but may be limited by aortic valve incompetence. We hypothesized that retrograde perfusion (RP) through the coronary sinus may provide more reliable perfusate delivery to the heart.

Production and NMR characterization of hyperpolarized (107,109)Ag complexes.

Both isotopes of silver, (107)Ag and (109)Ag, were simultaneously polarized by dynamic nuclear polarization (DNP), thus allowing large signal enhancements and the NMR characterization of Ag complexes in the millimolar concentration range. Since both isotopes have long relaxation times T(1), the hyperpolarized NMR signal of one isotope could still be observed even after the magnetization of the other isotope had been destroyed by radio-frequency pulses.

Transfer of hyperpolarization from long T1 storage nuclei to short T1 neighbors using FLOPSY-8.

Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation.

Ancillary care in public health intervention research in low-resource settings: researchers' practices and decision-making.

Little is known about researchers' practices regarding the provision of ancillary care (AC) in public health intervention studies they have conducted and the factors that influence their decisions about whether to provide ancillary care in low-resource settings. We conducted 52 in-person in-depth interviews with public health researchers. Data analysis was iterative and led to the identification of themes and patterns among themes.

Glucose is an ineffective substrate for preservation of machine perfused donor hearts.

Background: Machine perfusion with oxygenated preservation solution can support donor heart metabolism but the preservation solution should contain an oxidizable substrate to improve cellular energetics. We hypothesized that myocardial metabolism can be influenced by exogenous substrates in the preservation solution.

Methods: Eight groups of isolated rat hearts (n = 4/group) were perfused with University of Wisconsin Machine Perfusion Solution containing carbon 13 ((13)C) labeled glucose (2.