Evaluation of Hemoglobin A1c Criteria to Assess Preoperative Diabetes Risk in Cardiac Surgery Patients

Objective: Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. Methods: Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. Results: All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. Conclusions: In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90436/1/dia-2E2011-2E0074.pd

Lineage-specific gene radiations underlie the evolution of novel betalain pigmentation in Caryophyllales.

Betalain pigments are unique to the Caryophyllales and structurally and biosynthetically distinct from anthocyanins. Two key enzymes within the betalain synthesis pathway have been identified: 4,5-dioxygenase (DODA) that catalyzes the formation of betalamic acid and CYP76AD1, a cytochrome P450 gene that catalyzes the formation of cyclo-DOPA. We performed phylogenetic analyses to reveal the evolutionary history of the DODA and CYP76AD1 lineages and in the context of an ancestral reconstruction of pigment states we explored the evolution of these genes in relation to the complex evolution of pigments in Caryophylalles. Duplications within the CYP76AD1 and DODA lineages arose just before the origin of betalain pigmentation in the core Caryophyllales. The duplications gave rise to DODA-α and CYP76AD1-α isoforms that appear specific to betalain synthesis. Both betalain-specific isoforms were then lost or downregulated in the anthocyanic Molluginaceae and Caryophyllaceae. Our findings suggest a single origin of the betalain synthesis pathway, with neofunctionalization following gene duplications in the CYP76AD1 and DODA lineages. Loss of DODA-α and CYP76AD1-α in anthocyanic taxa suggests that betalain pigmentation has been lost twice in Caryophyllales, and exclusion of betalain pigments from anthocyanic taxa is mediated through gene loss or downregulation. [Correction added after online publication 13 May 2015: in the last two paragraphs of the Summary the gene name CYP761A was changed to CYP76AD1.].S.C. was supported by a grant to IRRI from the Bill and Melinda Gates Foundation and UKAID. This work was supported by a National Science Foundation award (grant numbers DEB 1354048 and DEB 1352907) to S.F.B., M.J.M. and S.A.S., and a NERC Independent Research Fellowship to S.F.B. The 1000 Plants (1KP) initiative, led by G.K.S.W., is funded by the Alberta Ministry of Enterprise and Advanced Education, Alberta Innovates Technology Futures (AITF), Innovates Centre of Research Excellence (iCORE), Musea Ventures and BGI-Shenzhen.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/nph.1344

Breast treatments with Axxent equipment.Comparison with Mammosite for skin, lung and heart dose

Poster Session [EP-1314] Purpose or Objective We have treated 250 patients at our center from May 2015 to September 2017 for breast cancer with Axxent (Xoft Inc.) intraoperativ e radiotherapy (IORT) following the inclusion parameters of the TARGIT study, in this work we compare the doses in the skin of the first 150 patients treated with the 50 kVp source with the skin doses they would have received using the Mammosite kit using an Ir192 source. Material and Methods To the 250 patients treated in our center after removing the tumor, the appropriate balloon size is chosen to cover the tumor area with a dose of 20 Gy on the ball oon surface, the sizes used range fro m 30-65 cm3, after which it is verified that the distance to skin from the 3 closest points of the balloon i s less than 10 mm and then the treatment is carried out with an average duration of 10.3 minutes being the volumes of 30 and 35 cm3 the most used due to the inclusion criteria of the procedure. Treatment plans are previously per formed in a Brachyvision treatment planning system (TPS) (Varian Inc.) for each of the possible volumes. In tur n, another plan is calculated with the Mammosite applicator and Ir192 source, from which the skin dose of each control point is estimated, compared to our results. We present also the cases of acute dermatitis seen for these first 150 patients in a time less than 6 months after the surgical act and irradiation. Results The differences in maximum skin dose for bot h types of treatment are 8.1 ± 1.2 Gy for the case of Mammosite and 5.7 ± 1.5 Gy for patients treated with electronic source, due to the difference in the depht dos e percentage of both types of treatment (Image 1). This, in turn, explains the very few cases of acute dermatitis at 6 months (8 cases of grade 2 and 2 cases of grade 3) (Image 2) with no recurrence to date.We also show the mean and maximum doses (expressed as percentage of prescribed dose) for the left lung and heart in cases of left breast tumor for the volumes of 30 and 35 cm3, which are the most common volumes in our hospital (70% of cases): LEFT LUNG (Left Breast tratment) AXXENT MAMMOSITE Maximun Dose (%PD) 20.4% 29.9% Mean Dose (%PD) 1.0% 3.9% HEART (Left Breast tratment) AXXENT MAMMOSITE Maximun Dose (%PD) 4.1% 10.4% Mean Dose (%PD) 0.8% 3.3% Conclusion It is concluded that the IORT treatments performed with the Axxent equipment with electronic source are a good alternative to those performed with Ir192 and our 250 patients treated to date to the good results presented by other centers are joined.In additi on to the low skin toxicity, there is no recurrence in patients treated so far, which makes us very optimistic about the results

Oxidative discolouration in whole-head and cut lettuce: biochemical and environmental influences on a complex phenotype and potential breeding strategies to improve shelf-life

Lettuce discolouration is a key post-harvest trait. The major enzyme controlling oxidative discolouration has long been considered to be polyphenol oxidase (PPO) however, levels of PPO and subsequent development of discolouration symptoms have not always correlated. The predominance of a latent state of the enzyme in plant tissues combined with substrate activation and contemporaneous suicide inactivation mechanisms are considered as potential explanations for this phenomenon. Leaf tissue physical properties have been associated with subsequent discolouration and these may be influenced by variation in nutrient availability, especially excess nitrogen and head maturity at harvest. Mild calcium and irrigation stress has also been associated with a reduction in subsequent discolouration, although excess irrigation has been linked to increased discolouration potentially through leaf physical properties. These environmental factors, including high temperature and UV light intensities, often have impacts on levels of phenolic compounds linking the environmental responses to the biochemistry of the PPO pathway. Breeding strategies targeting the PALand PPOpathway biochemistry and environmental response genes are discussed as a more cost-effective method of mitigating oxidative discolouration then either modified atmosphere packaging or post-harvest treatments, although current understanding of the biochemistry means that such programs are likely to be limited in nature and it is likely that they will need to be deployed alongside other methods for the foreseeable future

A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project

Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don't always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBPK modelling to predict transfer of medication into the human milk. However, reliable data as input for PBPK models is often missing. The iterative development of in vitro, animal in vivo and PBPK modelling methods seems to be a promising approach. Human in vitro models will deliver essential data on the transepithelial transport of medication, whereas the combination of animal in vitro and in vivo methods will deliver information to establish accurate in vitro/in vivo extrapolation (IVIVE) algorithms and mechanistic insights. Such a non-clinical platform will be developed and thoroughly evaluated by the Innovative Medicines Initiative ConcePTION

Elucidating the role of shape anisotropy in faceted magnetic nanoparticles using biogenic magnetosomes as a model

Shape anisotropy is of primary importance to understand the magnetic behavior of nanoparticles, but a rigorous analysis in polyhedral morphologies is missing. In this work, a model based on finite element techniques has been developed to calculate the shape anisotropy energy landscape for cubic, octahedral, and truncated octahedral morphologies. In all cases, a cubic shape anisotropy is found that evolves to quasi uniaxial anisotropy when the nanoparticle is elongated amp; 8805;2 . This model is tested on magnetosomes, amp; 8764;45 nm truncated octahedral magnetite nanoparticles forming a chain inside Magnetospirillum gryphiswaldense MSR 1 bacteria. This chain presents a slightly bent helical configuration due to a 20 tilting of the magnetic moment of each magnetosome out of chain axis. Electron cryotomography images reveal that these magnetosomes are not ideal truncated octahedrons but present amp; 8776;7.5 extrusion of one of the 001 square faces and amp; 8776;10 extrusion of an adjacent 111 hexagonal face. Our model shows that this deformation gives rise to a quasi uniaxial shape anisotropy, a result of the combination of a uniaxial Ksh u 7 kJ m amp; 8722;3 and a cubic Ksh c 1.5 kJ m amp; 8722;3 contribution, which is responsible for the 20 tilting of the magnetic moment. Finally, our results have allowed us to accurately reproduce, within the framework of the Landau Lifshitz Gilbert model, the experimental AC loops measured for these magnetotactic bacteri

Analysis of results of effective dose estimation obtained from RADAR 2017 dose assessment model for nuclear medicine procedures

EP-296 Aim/Introduction: To analyze the results of effective dose (E) estimation of the most frequent procedures using photon emitters in Nuclear Medicine, obtained from RADAR 2017 dose assessment model. To compare these results with those obtained from ICRP 128 (2015) recommendations, and to assess how using each dose assessment model can change E results. Materials and Methods: E estimation data was collected from photon emitter procedures performed during the last year in our department, obtained from RADAR 2017 dose estimation model for age groups: = 1 year old; >1-5 years old ; >5- 10 years old, >10- 15 years old and adults. Injected activity was the one recommended by international guidelines and EANM Pediatric and Dosimetry Committees. Hybrid exams (SPECT / CT) and procedures for which there is no RADAR 2017 dosimetry estimation were excluded. Results for (E) were compared with those obtained by using ICRP 128 (2015) recommendations. Results: With RADAR 2017 dose evaluation model we obtained a lower mean value of E on most of the procedures that were analyzed, being significantly lower for Renogram, Renal scintigraphy on >10-15 years old, Thyroid scintigraphy, Meckel’s scan and Bone Scan (0.12 to 1.16 mSv, 25% to 67%). Brain perfusion and Renal scintigraphy on ages under 10 obtained a significantly greater difference for E (0.33 to 2.85 mSv, 26% to 29%). Conclusion: These results are an updated collection of estimated E values for photon-emitting radiopharmaceuticals commonly used in Nuclear Medicine, considering RADAR 2017 dose assessment model compared to ICRP 128) recommendations. Methodological changes on estimation lead to lower E for most of diagnostic procedures using photon emitters, this is of special interest for patients undergoing repeated ionizing radiation (dosimetry history)

Why Were More Than 200 Subjects Required to Demonstrate the Bioequivalence of a New Formulation of Levothyroxine with an Old One?

At the request of French Regulatory Authorities, a new formulation of Levothyrox® was licensed in France in 2017, with the objective of avoiding the stability deficiencies of an existing licensed formulation. Before launching the new formulation, an average bioequivalence (ABE) trial was conducted, having enrolled 204 subjects and selected for interpretation a narrow a priori bioequivalence range of 0.90–1.11. Bioequivalence was concluded. In a previous publication, we questioned the ability of an ABE trial to guarantee the switchability within patients of the new and old levothyroxine formulations. It was suggested that the two formulations should be compared using the conceptual framework of individual bioequivalence. The present paper is a response to those claiming that, despite the fact that ABE analysis does not formally address the switchability of the two formulations, future patients will nevertheless be fully protected. The basis for this claim is that the ABE study was established in a large trial and analyzed using a stringent a priori acceptance interval of equivalence. These claims are questionable, because the use of a very large number of subjects nullifies the implicit precautionary intention of the European guideline when, for a Narrow Therapeutic Index drug, it recommends shortening the a priori acceptance interval from 0.80–1.25 to 0.90–1.11

Tuning the Magnetic Response of Magnetospirillum magneticum by Changing the Culture Medium A Straightforward Approach to Improve Their Hyperthermia Efficiency

Magnetotactic bacteria Magnetospirillum magneticum AMB 1 have been cultured using three different media magnetic spirillum growth medium with Wolfe s mineral solution MSGM W , magnetic spirillum growth medium without Wolfe s mineral solution MSGM W , and flask standard medium FSM . The influence of the culture medium on the structural, morphological, and magnetic characteristics of the magnetosome chains biosynthesized by these bacteria has been investigated by using transmission electron microscopy, X ray absorption spectroscopy, and X ray magnetic circular dichroism. All bacteria exhibit similar average size for magnetosomes, 40 45 nm, but FSM bacteria present slightly longer subchains. In MSGM W bacteria, Co2 ions present in the medium substitute Fe2 ions in octahedral positions with a total Co doping around 4 5 . In addition, the magnetic response of these bacteria has been thoroughly studied as functions of both the temperature and the applied magnetic field. While MSGM W and FSM bacteria exhibit similar magnetic behavior, in the case of MSGM W, the incorporation of the Co ions affects the magnetic response, in particular suppressing the Verwey amp; 8764;105 K and low temperature amp; 8764;40 K transitions and increasing the coercivity and remanence. Moreover, simulations based on a Stoner Wolhfarth model have allowed us to reproduce the experimentally obtained magnetization versus magnetic field loops, revealing clear changes in different anisotropy contributions for these bacteria depending on the employed culture medium. Finally, we have related how these magnetic changes affect their heating efficiency by using AC magnetometric measurements. The obtained AC hysteresis loops, measured with an AC magnetic field amplitude of up to 90 mT and a frequency, f, of 149 kHz, reveal the influence of the culture medium on the heating properties of these bacteria below 35 mT, MSGM W bacteria are the best heating mediators, but above 60 mT, FSM and MSGM W bacteria give the best heating results, reaching a maximum heating efficiency or specific absorption rate SAR of SAR f amp; 8776; 12 W g 1 kHz