Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Metabolic outcome of female mice exposed to a mixture of low-dose pollutants in a diet-induced obesity model.

Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic impact of food pollutants using a recently set up model in which mice are life-long fed a high-fat/high-sucrose diet (HFSD) with/without common food pollutants shown to exhibit metabolic disrupting activities. Specifically, this mixture comprised bisphenol A, dioxin, polychlorobiphenyl PCB153, and phthalate and was added in HFSD at doses resulting in mice exposure at the Tolerable Daily Intake dose range for each pollutant. We herein focused on the 7-week-old females which exhibited early signs of obesity upon HFSD feeding. We observed no signs of toxicity and no additional weight gain following exposure to the mixture but alleviated HFSD-induced glucose intolerance in the absence of alteration of gluconeogenesis and steatosis. It suggested that the observed metabolic improvement was more likely due to effects on muscle and/or adipose tissues rather than on the liver. Consistently, female mice exhibited enhanced lean/fat mass ratio and skeletal muscle insulin sensitivity. Moreover, expression levels of inflammatory markers were reduced in adipose tissue at 7 but enhanced at 12 weeks of age in agreement with the inverse alterations of glucose tolerance observed at these ages upon pollutant exposure in the HFSD-fed females. Collectively, these data suggest apparent biphasic effects of pollutants upon HFSD feeding along with obesity development. These effects were not observed in males and may depend on interactions between diet and pollutants

Solvent Dynamical Behavior in an Organogel Phase As Studied by NMR Relaxation and Diffusion Experiments

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Western blot analysis of the ratio between phosphorylated PKB/AKT versus total PKB/AKT in the gastrocnemius muscle removed from F1-HF0 and F1-HFp mice stimulated or not by insulin (the fold stimulation by insulin, relative to the mean of the corresponding control without insulin was assigned above each band shown).

<p>For quantification, each blot has been hybridized to α-tubulin and the graphs below represent means ± SE; *p<0.05 relatively to the F1-HF0 group; n = 7–8 mice.</p

mRNA expression of Nr1c3, AdipoQ, CD68 and genes encoding inflammatory markers in the subcutaneous adipose tissues of 7 and 12 wk-old female mice fed HFSD.

<p>Results are means ± SE; <i>p</i> values are reported in the figure for significance; n = 8–12 mice for Nr1c3, Tnfα, CD68, AdipoQ and Il6 and n = 5 mice for Ccl5 and Il1b in the samples from 7-wk old mice; n = 5–6 mice for Nr1c3 and n = 9–14 mice for the other genes in the samples from 12-wk old mice.</p

(A) Effect of the mixture of pollutants on hepatic mRNA expression of xenobiotic nuclear receptors; (B) Analysis by Western blot of the ratio between phosphorylated PKB/AKT versus total PKB/AKT in liver removed from F1-HF0 and F1-HFp mice stimulated or not by insulin.

<p>For quantification, each blot has been hybridized to α-tubulin and the graphs below represent means ± SE; n = 7–8 mice. (C) and (D) Hepatic expression of Nr1c1 and of several PPARα-regulated genes (C) and of genes encoding proteins involved in lipogenesis (D). Results are means ± SE; *p<0.05 relatively to the F1-HF0 group; n = 7 mice in (A), (C) and (D).</p

mRNA expression of Nr1c3 and genes encoding inflammatory markers in visceral adipose tissues in 7 wk-old female mice fed HFSD.

<p>Results are means ± SE; *p<0.05 relatively to the F1-HF0 group; n = 9–10 mice for Nr1c3, Tnfα and Il6; n = 5 mice for Ccl5 and Il1b.</p

MRI figures and graphs.

<p>(A) Representative coronal fat image of females fed standard chow and from F1-HF0 and F1-HFp groups, showing the relatively less important fat mass in the F1-HFp group, especially in the subcutaneous localization. These differences were confirmed by the whole-body spectrum analysis, and by the subcutaneous (sc) and visceral fat mass quantification in both groups (B). Results are means ± SE (n = 6 mice/group). *p<0.05 relatively to the F1-HF0 group.</p

Glucose Tolerance Tests (GTTs) performed on 7 wk-old (A) and 12 wk-old (B) F1 female mice fed HFS diet containing (F1-HFp) or not (F1-HF0) the mixture of pollutants, or standard chow (Standard).

<p>Above each GTT curve, are shown the AUCs calculated from the GTT curves. Results are means ± SE of n = 5 (Standard), 7(HF0) and 9 (HFP) litters in (A) and n = 3 litters in B; *p<0.05 relatively to the F1-HF0 group.</p