Fat oxidation kinetics during exercise in obese individuals

Introduction An impaired ability to oxidize fat may be a factor in the obesity's aetiology (3). Moreover, the exercise intensity (Fatmax) eliciting the maximal fat oxidation rate (MFO) was lower in obese (O) compared with lean (L) individuals (4). However, difference in fat oxidation rate (FOR) during exercise between O and L remains equivocal and little is known about FORs during high intensities (>60% ) in O compared with L. This study aimed to characterize fat oxidation kinetics over a large range of intensities in L and O. Methods 12 healthy L [body mass index (BMI): 22.8±0.4] and 16 healthy O men (BMI: 38.9±1.4) performed submaximal incremental test (Incr) to determine whole-body fat oxidation kinetics using indirect calorimetry. After a 15-min resting period (Rest) and 10-min warm-up at 20% of maximal power output (MPO, determined by a maximal incremental test), the power output was increased by 7.5% MPO every 6-min until respiratory exchange ratio reached 1.0. Venous lactate and glucose and plasma concentration of epinephrine (E), norepinephrine (NE), insulin and non-esterified fatty acid (NEFA) were assessed at each step. A mathematical model (SIN) (1), including three variables (dilatation, symmetry, translation), was used to characterize fat oxidation (normalized by fat-free mass) kinetics and to determine Fatmax and MFO. Results FOR at Rest and MFO were not significantly different between groups (p≥0.1). FORs were similar from 20-60% (p≥0.1) and significantly lower from 65-85% in O than in L (p≤0.04). Fatmax was significantly lower in O than in L (46.5±2.5 vs 56.7±1.9 % respectively; p=0.005). Fat oxidation kinetics was characterized by similar translation (p=0.2), significantly lower dilatation (p=0.001) and tended to a left-shift symmetry in O compared with L (p=0.09). Plasma E, insulin and NEFA were significantly higher in L compared to O (p≤0.04). There were no significant differences in glucose, lactate and plasma NE between groups (p≥0.2). Conclusion The study showed that O presented a lower Fatmax and a lower reliance on fat oxidation at high, but not at moderate, intensities. This may be linked to a: i) higher levels of insulin and lower E concentrations in O, which may induce blunted lipolysis; ii) higher percentage of type II and a lower percentage of type I fibres (5), and iii) decreased mitochondrial content (2), which may reduce FORs at high intensities and Fatmax. These findings may have implications for an appropriate exercise intensity prescription for optimize fat oxidation in O. References 1. Cheneviere et al. Med Sci Sports Exerc. 2009 2. Holloway et al. Am J Clin Nutr. 2009 3. Kelley et al. Am J Physiol. 1999 4. Perez-Martin et al. Diabetes Metab. 2001 5. Tanner et al. Am J Physiol Endocrinol Metab. 2002

The Coordinated Radio and Infrared Survey for High-Mass Star Formation (The CORNISH Survey). I. Survey Design

We describe the motivation, design, and implementation of the CORNISH survey, an arcsecondresolution radio continuum survey of the inner galactic plane at 5 GHz using the Very Large Array (VLA). It is a blind survey coordinated with the northern SpitzerGLIMPSE I region covering 10° massive star formation. A sensitivity around 2 mJy will allow the automatic distinction between radio-loud and radio-quiet midIR sources found in the Spitzersurveys. This survey has many legacy applications beyond star formation, including evolved stars, active stars and binaries, and extragalactic sources. The CORNISH survey for compact ionized sources complements other Galactic plane surveys that target diffuse and nonthermal sources, as well as atomic and molecular phases to build up a complete picture of the interstellar medium in the Galaxy.

Can a Halo CME from the limb be geoeffective?

The probability for a halo coronal mass ejection (CME) to be geoeffective is assumed to be higher the closer the CME launch site is located to the solar central meridian. However, events far from the central meridian may produce severe geomagnetic storms, like the case in April 2000. In this work, we study the possible geoeffectiveness of full halo CMEs with the source region situated at solar limb. For this task, we select all limb full halo (LFH) CMEs that occurred during solar cycle 23, and we search for signatures of geoeffectiveness between 1 and 5 days after the first appearance of each CME in the LASCO C2 field of view. When signatures of geomagnetic activity are observed in the selected time window, interplanetary data are carefully analyzed in order to look for the cause of the geomagnetic disturbance. Finally, a possible association between geoeffective interplanetary signatures and every LFH CME in solar cycle 23 is checked in order to decide on the CME's geoeffectiveness. After a detailed analysis of solar, interplanetary, and geomagnetic data, we conclude that of the 25 investigated events, there are only four geoeffective LFH CMEs, all coming from the west limb. The geoeffectiveness of these events seems to be moderate, turning to intense in two of them as a result of cumulative effects from previous mass ejections. We conclude that ejections from solar locations close to the west limb should be considered in space weather, at least as sources of moderate disturbances.

A statistical methodology for the comparison of blue gel pen inks analyzed by laser desorption/ionization mass spectrometry

A statistical methodology for the objective comparison of LDI-MS mass spectra of blue gel pen inks was evaluated. Thirty-three blue gel pen inks previously studied by RAMAN were analyzed directly on the paper using both positive and negative mode. The obtained mass spectra were first compared using relative areas of selected peaks using the Pearson correlation coefficient and the Euclidean distance. Intra-variability among results from one ink and inter-variability between results from different inks were compared in order to choose a differentiation threshold minimizing the rate of false negative (i.e. avoiding false differentiation of the inks). This yielded a discriminating power of up to 77% for analysis made in the negative mode. The whole mass spectra were then compared using the same methodology, allowing for a better DP in the negative mode of 92% using the Pearson correlation on standardized data. The positive mode results generally yielded a lower differential power (DP) than the negative mode due to a higher intra-variability compared to the inter-variability in the mass spectra of the ink samples.

Hydrogen sulfide measurement by headspace-gas chromatography-mass spectrometry (HS-GC-MS): application to gaseous samples and gas dissolved in muscle.

The aim of our study was to present a new headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable to the routine determination of hydrogen sulfide (H(2)S) concentrations in biological and gaseous samples. The primary analytical drawback of the GC/MS methods for H(2)S measurement discussed in the literature was the absence of a specific H(2)S internal standard required to perform quantification. Although a deuterated hydrogen sulfide (D(2)S) standard is currently available, this standard is not often used because this standard is expensive and is only available in the gas phase. As an alternative approach, D(2)S can be generated in situ by reacting deuterated chloride with sodium sulfide; however, this technique can lead to low recovery yield and potential isotopic fractionation. Therefore, N(2)O was chosen for use as an internal standard. This method allows precise measurements of H(2)S concentrations in biological and gaseous samples. Therefore, a full validation using accuracy profile based on the β-expectation tolerance interval is presented. Finally, this method was applied to quantify H(2)S in an actual case of H(2)S fatal intoxication.

Multiplex liquid chromatography-tandem mass spectrometry assay for simultaneous therapeutic drug monitoring of ribavirin, boceprevir, and telaprevir.

New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

Impact of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry on the Clinical Management of Patients With Gram-negative Bacteremia: A Prospective Observational Study.

Background. Early identification of pathogens from blood cultures using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry may optimize the choice of empirical antibiotic therapy in the setting of bloodstream infections. We aimed to assess the impact of this new technology on the use of antibiotic treatment in patients with gram-negative bacteremia. Methods. We conducted a prospective observational study from January to December 2010 to evaluate the sequential and separate impacts of Gram stain reporting and MALDI-TOF bacterial identification performed on blood culture pellets in patients with gram-negative bacteremia. The primary outcome was the impact of MALDI-TOF on empirical antibiotic choice. Results. Among 202 episodes of gram-negative bacteremia, Gram stain reporting had an impact in 42 cases (20.8%). MALDI-TOF identification led to a modification of empirical therapy in 71 of all 202 cases (35.1%), and in 16 of 27 cases (59.3%) of monomicrobial bacteremia caused by AmpC-producing Enterobacteriaceae. The most frequently observed impact was an early appropriate broadening of the antibiotic spectrum in 31 of 71 cases (43.7%). In total, 143 of 165 episodes (86.7%) of monomicrobial bacteremia were correctly identified at genus level by MALDI-TOF. Conclusions. In a low prevalence area for extended spectrum betalactamases (ESBL) and multiresistant gram-negative bacteria, MALDI-TOF performed on blood culture pellets had an impact on the clinical management of 35.1% of all gram-negative bacteremia cases, demonstrating a greater impact than Gram stain reporting. Thus, MALDI-TOF could become a vital second step beside Gram stain in guiding the empirical treatment of patients with bloodstream infection.

Leaf senescence of common bean plants as affected by soil phosphorus supply

Responses of leaf senescence to P supply could constitute adaptive mechanisms for plant growth under P-limiting conditions. The aim of this study was to evaluate the effects of soil P supply on leaf senescence of common bean (Phaseolus vulgaris L.). Eight P levels, ranging from 5 to 640 mg kg-1 P, were applied to pots containing four bean plants of cultivar Carioca in 10 kg of an Oxic Haplustult soil. Attached leaves were counted weekly, abscised leaves were collected every other day, and seeds were harvested at maturity. The number of live leaves increased until 48 days after emergence (DAE) and decreased afterwards, irrespective of applied P levels. At lower applied P levels, the initial increase and the final decrease of leaf number was weak, whereas at higher applied P levels the leaf number increased intensively at the beginning of the growth cycle and decreased strongly after 48 DAE. Dry matter and P accumulated in senesced leaves increased as soil P levels increased until 61 DAE, but differences between P treatments narrowed thereafter. The greatest amounts of dry mass and P deposited by senesced leaves were observed at 48-54 DAE for high P levels, at 62-68 DAE for intermediate P levels and at 69-76 DAE for low P levels. These results indicate that soil P supply did not affect the stage of maximal leaf number and the beginning of leaf senescence of common bean plants, but the stage of greatest deposition of senesced leaves occurred earlier in the growth cycle as the soil P supply was raised.

No use for waist-for-height ratio in addition to body mass index to identify children with elevated blood pressure.

Abstract Background. In children, waist-for-height ratio (WHtR) has been proposed to identify subjects at higher risk of cardiovascular diseases. The utility of WHtR to identify children with elevated blood pressure (BP) is unclear. Design. Cross-sectional population-based study of schoolchildren. Methods. Weight, height, waist circumference and BP were measured in all sixth-grade schoolchildren of the canton de Vaud (Switzerland) in 2005/06. WHtR was computed as waist [cm]/height [cm]. Elevated BP was defined according to sex-, age- and height-specific US reference data. The area under the receiver operating characteristic curve (AUC) statistic was computed to compare the ability of body mass index (BMI) z-score and WHtR, alone or in combination, to identify children with elevated BP. Results. 5207 children participated (76% response) [2621 boys, 2586 girls; mean (± SD) age, 12.3 ± 0.5 years; range: 10.1-14.9]. The prevalence of elevated BP was 11%. Mean WHtR was 0.44 ± 0.05 (range: 0.29- 0.77) and 11% had high WHtR (> 0.5). BMI z-score and WHtR were strongly correlated (Spearman correlation coefficient r = 0.76). Both indices were positively associated with elevated BP. AUCs for elevated BP was relatively low for BMI z-score (0.62) or for WHtR (0.62), and was not substantially improved when both indices were considered together (0.63). Conclusions. The ability of BMI z-score or WHtR to identify children aged 10-14 with elevated BP was weak. Adding WHtR did not confer additional discriminative power to BMI alone. These findings do not support the measurement of WHtR in addition to BMI to identify children with elevated BP.

Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice

In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication.

Transplanted beta cell response to increased metabolic demand. Changes in beta cell replication and mass

We determined the capacity of transplanted beta cells to modify their replication and mass when stimulated by changes in metabolic demand. Five groups of Lewis rats were studied: group 1 (Tx-Px) had a 95% pancreatectomy 14 d after transplantation of 500 islets; group 2 (Px-Tx) had a 95% pancreatectomy 14 d before transplantation of 500 islets; group 3 (Tx) was transplanted with 500 islets; group 4 (Px) had a 95% pancreatectomy; and group 5 (normal) was neither transplanted nor pancreatectomized. Blood glucose was normal in Tx-Px and Tx groups at all times. Px-Tx and Px groups developed severe hyperglycemia after pancreatectomy that was corrected in Px-Tx group in 83% of rats 28 d after transplantation. Replication of transplanted beta cells increased in Tx-Px (1.15 +/- 0.12%) and Px-Tx (0.85 +/- 0.12%) groups, but not in Tx group (0.64 +/- 0.07%) compared with normal pancreatic beta cells (0.38 +/- 0.05%) (P < 0.001). Mean beta cell size increased in Tx-Px (311 +/- 14 microns2) and Px-Tx (328 +/- 13 microns2) groups compared with Tx (252 +/- 12 microns2) and normal (239 +/- 9 microns2) groups (P < 0.001). Transplanted beta cell mass increased in Tx-Px (1.87 +/- 0.51 mg) and Px-Tx (1.55 +/- 0.21 mg) groups compared with Tx group (0.78 +/- 0.17 mg) (P < 0.05). In summary, changes in transplanted beta cells prevented the development of hyperglycemia in Tx-Px rats. Transplanted beta cells responded to increased metabolic demand increasing their beta cell mass.

The ontogeny of sexual size dimorphism of a moth: when do males and females grow apart?

Sexual dimorphism in body size (sexual size dimorphism) is common in many species. The sources of selection that generate the independent evolution of adult male and female size have been investigated extensively by evolutionary biologists, but how and when females and males grow apart during ontogeny is poorly understood. Here we use the hawkmoth, Manduca sexta, to examine when sexual size dimorphism arises by measuring body mass every day during development. We further investigated whether environmental variables influence the ontogeny of sexual size dimorphism by raising moths on three different diet qualities (poor, medium and high). We found that size dimorphism arose during early larval development on the highest quality food treatment but it arose late in larval development when raised on the medium quality food. This female-biased dimorphism (females larger) increased substantially from the pupal-to-adult stage in both treatments, a pattern that appears to be common in Lepidopterans. Although dimorphism appeared in a few stages when individuals were raised on the poorest quality diet, it did not persist such that male and female adults were the same size. This demonstrates that the environmental conditions that insects are raised in can affect the growth trajectories of males and females differently and thus when dimorphism arises or disappears during development. We conclude that the development of sexual size dimorphism in M. sexta occurs during larval development and continues to accumulate during the pupal/adult stages, and that environmental variables such as diet quality can influence patterns of dimorphism in adults.

Mass conservative three-dimensional water tracer distribution from Markov chain Monte Carlo inversion of time-lapse ground-penetrating radar data

Time-lapse geophysical measurements are widely used to monitor the movement of water and solutes through the subsurface. Yet commonly used deterministic least squares inversions typically suffer from relatively poor mass recovery, spread overestimation, and limited ability to appropriately estimate nonlinear model uncertainty. We describe herein a novel inversion methodology designed to reconstruct the three-dimensional distribution of a tracer anomaly from geophysical data and provide consistent uncertainty estimates using Markov chain Monte Carlo simulation. Posterior sampling is made tractable by using a lower-dimensional model space related both to the Legendre moments of the plume and to predefined morphological constraints. Benchmark results using cross-hole ground-penetrating radar travel times measurements during two synthetic water tracer application experiments involving increasingly complex plume geometries show that the proposed method not only conserves mass but also provides better estimates of plume morphology and posterior model uncertainty than deterministic inversion results.