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In the dairy cow, negative energy balance affects milk yield and composition as well as animal health. Studying the effects of negative energy balance on dairy cow milk production is thus essential. Feed restriction (FR) experiments attempting to reproduce negative energy balance by reducing the quantity or quality of the diet were conducted in order to better describe the animal physiology changes. The study of FR is also of interest since with climate change issues, cows may be increasingly faced with periods of drought leading to a shortage of forages. The aim of this article is to review the effects of FR during lactation in dairy cows to obtain a better understanding of metabolism changes and how it affects mammary gland activity and milk production and composition. A total of 41 papers studying FR in lactating cows were used to investigate physiological changes induced by these protocols. FR protocols affect the entire animal metabolism as indicated by changes in blood metabolites such as a decrease in glucose concentration and an increase in non-esterified fatty acid or β-hydroxybutyrate concentrations; hormonal regulations such as a decrease in insulin and insulin-like growth factor I or an increase in growth hormone concentrations. These variations indicated a mobilization of body reserve in most studies. FR also affects mammary gland activity through changes in gene expression and could affect mammary cell turnover through cell apoptosis, cell proliferation, and exfoliation of mammary epithelial cells into milk. Because of modifications of the mammary gland and general metabolism, FR decreases milk production and can affect milk composition with decreased lactose and protein concentrations and increased fat concentration. These effects, however, can vary widely depending on the type of restriction, its duration and intensity, or the stage of lactation in which it takes place. Finally, to avoid yield loss and metabolic disorders, it is important to identify reliable biomarkers to monitor energy balance., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Purpose: Cytarabine, a key chemotherapy agent for acute myeloid leukemia (AML) treatment, is deaminated into inactive uracil-arabinoside by cytidine deaminase. This deamination leads to samples stability issues with respect to clinical pharmacokinetic trials. The aim of our study was to study in vitro cytarabine stability in blood samples obtained from AML patients., Methods: Cytarabine quantification was performed using a fully validated LC/MS/MS method. In vitro cytarabine stability was assessed at room temperature over 24 h in samples coming from 14 AML patients and 7 control patients (CTRL) with no hematological malignancy. In vitro concentrations versus time data were analyzed using a noncompartmental approach., Results: Cytarabine in vitro area under the curve (AUC IVlast ) was 22-fold higher in AML samples as compared to CTRL samples (AML mean (standard deviation (SD)), 51,829 (27,004) h ng/mL; CTRL mean (SD), 2356 (1250) h ng/mL, p = 0.00019). This increase was associated with a prolonged in vitro degradation half-life (t 1/2IVdeg AML mean (SD), 15 (11.8) h; CTRL mean (SD), 0.36 (0.37) h, p = 0.0033). Multiple linear regression analysis showed that AML diagnosis significantly influenced t 1/2IVdeg and AUC IVlas relationship., Conclusion: Cytarabine stability is higher in AML than in CTRL samples. The absence of correlation between t 1/2IVdeg and AUC IVlast in AML samples suggests that in vitro cytarabine degradation in AML is complex. These results open perspectives including the evaluation of the clinical relevance and the involved molecular mechanisms.

Obstructive sleep apnoea syndrome (OSAS) patients do not report breathing discomfort in spite of abnormal upper airway mechanics. We studied respiratory sensations in OSAS patients without and with mandibular advancement device (MAD). Fifty-seven moderate to severe non obese OSAS patients were asked about breathing discomfort using visual analogue scales (VAS) in the sitting position (VAS-1), after lying down (VAS-2), then with MAD (VAS-3). Awake critical closing pressure (awake Pcrit) was measured in 15 patients without then with MAD. None of the patients reported breathing discomfort when sitting but 19 patients (33%) did when lying (VAS-2: -20% or less). A feeling of "easier breathing" with MAD was observed and was more marked in patients reporting breathing discomfort when supine (VAS-3: +66.0% [49.0; 89.0]) than in those not doing so (VAS-3: +28.5% [1.0; 56.5], p = 0.007). MAD-induced change in awake Pcrit was correlated to VAS-3. In conclusion, MAD revealed "latent dyspnea" related to the severity of upper airways mechanics abnormalities in OSAS patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: For oncological evaluations, quantitative radiology gives clinicians significant insight into patients' response to therapy. In regard to the Response Evaluation Criteria in Solid Tumours (RECIST), the classification of disease evolution partly consists in applying thresholds to the measurement of the relative change of tumour. In the case of tumour volumetry, response thresholds have not yet been established. This study proposes and validates a model for calculating thresholds for the detection of minimal tumour change when using the volume of pulmonary lesions on CT as imaging biomarker., Methods: Our work is based on the reliability analysis of tumour volume measurements documented by the Quantitative Imaging Biomarker Alliance. Statistics of measurements were entered into a multi-parametric mathematical model of the relative changes derived from the Geary-Hinkley transformation. The consistency of the model was tested by comparing modelled thresholds against Monte Carlo simulations of tumour volume measurements with additive random error. The model has been validated by repeating measurements on real patient follow ups., Results: For unchanged tumour volume, relying on a normal distribution of error, the agreement between model and simulations featured a type I error of 5.25%. Thus, we established that a threshold of 35% of volume reduction corresponds to a partial response (PR) and a 55% volume increase corresponds to progressive disease (PD). Changes between -35 and +55% are categorized as stable disease (SD). Tested on real clinical data, 97.1% [95.7; 98.0] of assessments fall into the range of variability predicted by our model of confidence interval., Conclusions: Our study indicates that the Geary Hinkley model, using published statistics, is appropriate to predict response thresholds for the volume of pulmonary lesions on CT.