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An impaired intestinal epithelial barrier is thought to be a major factor in the pathogenesis of human inflammatory bowel disease (IBD). IBD is frequently investigated by inducing a damaged barrier in murine models of colitis. This can be done by feeding mice with dextran sulfate sodium (DSS) polymers in their drinking water. Refinement measures should focus on alleviating unnecessary suffering during this probably painful condition. Appropriate parameters are needed to decide when to terminate the experiments. Our aim was to investigate whether a change in burrowing behaviour is a sensitive measure of animal welfare in murine models of colitis. Acute colitis was induced in C57BL/6 mice with 2.0% DSS over nine days. The burrowing test is based on the species-typical behaviour of mice to spontaneously displace items from tubes within their home cage. As a burrowing apparatus, a water bottle (250 mL, 150 mm length, 55 mm diameter) filled with 138–142 g of pellets of the animal’s diet was used. The presence of intestinal inflammation as a result of acute DSS-induced colitis was confirmed by a decrease in body weight, colon length and an increase of murine endoscopic index of colitis severity, histological score and spleen weight in the group receiving DSS as compared with the control group. An onset of intestinal inflammation correlated with a significant decrease in burrowing behaviour (P < 0.05). Altered adrenal gland histology indicated stress as a result of acute colitis. Our findings provide evidence that changes of spontaneous burrowing behaviour correlate with the onset of inflammation in acute DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Polydimethylsiloxane (PDMS) is an organic silicone with a viscoelastic behavior suitable for use in engineering. This material presents substantial changes in its properties depending on the temperature and the flow rate: at high temperatures or high flow rates, it behaves as a viscous liquid; whereas, at low temperatures or low flow rates, it behaves as an elastic solid. The lack of accurate information about the modifications in PDMS under thermal changes affects the design of transducers (both sensors and actuators) based on this material and also their calibration. In this study, 10:1 base-agent mixing ratio was analyzed in a 20 °C to 50 °C temperature range to assess the ultrasonic P-wave properties (velocity, attenuation, and variation of both with the frequency) and hence complex elastic modulii of this material under a temperature dependent environment. P-wave velocity and attenuation were extracted for every temperature step in a 3–7 MHz frequency range which is the typical range for medical applications. Acoustic dispersion of PDMS properties such as velocity and attenuation in a pulse-echo set up were analyzed to also compute attenuation coefficient, temperature and frequency dependent models and complex modulus. • Temperature affects PDMS p-wave velocity with a slope of 3.2 m/s/°C at 5 MHz. • Temperature affects PDMS p-wave attenuation with a slope of 1 m−1/°C at 5 MHz. • The dispersion in PDMS is small, with less than 2% variation in p-wave velocity. • Models of velocity and attenuation including frequency and temperature are proposed. • Complex modulus considering frequency and temperature are calculated. [ABSTRACT FROM AUTHOR]

Aim It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (α CGRP), known to be released from contracting skeletal muscles, is key at this remodelling. Methods The hypertrophic effect of α CGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. Results While α CGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP−/− mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors ( CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in α CGRP−/− mice and elevated in CLR-tg. Transcriptional changes seen in α CGRP−/− (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. Conclusions Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, α CGRP agonists might be beneficial in heart failure patients. [ABSTRACT FROM AUTHOR]

Ventricular end-diastolic volume (EDV) is an important parameter for monitoring patients with heart pumps, and for informing an algorithm to adapt the pump speed in a smart way. Continuous information on the EDV is unavailable to date. We hypothesize that the depolarization amplitude of the non-contact intra-cardiac electromyogram (iEMG) is physically related to the EDV. Thus, it could serve as a useful measure for predicting EDV in these patients. The study was performed in six pigs while undergoing a series of significant changes in hemodynamic states. Four conventional pacemaker electrodes measured the far-field iEMG inside the left ventricular blood pool, using a novel unipolar amplifier. Simultaneously, measurements of preload and hematocrit were recorded. The proposed EDV predictor was tested for statistical significance using a mixed effect model and associated confidence intervals. A statistically significant (p<0.005) negative correlation was confirmed between the amplitude of the iEMG and the EDV measured by electric impedance at a slope of -0.063 (-0.066, -0.060) mV/mL. The influence of the hematocrit was not found significant. All measurements of the four distinct electrodes yielded comparable results. The amplitude of the iEMG proved a significant, independent predictor of the EDV. Electrodes are simple to integrate into the cannula of a heart pump. Because of their simplicity, electrodes shall be incorporated in the inflow cannula of heart pumps. Given the manifold determinants of the depolarization amplitude, a combination with a mechanical signal, such as pump flow, is likely to further increase robustness. In this way, the iEMG has the potential to inform the clinician about the state of the patient in real-time and to control the pump in a smart way. [ABSTRACT FROM AUTHOR]