Personalized intermittent pneumatic calf compression frequency for augmenting foot blood perfusion: The optimized effect and a personalized mode predicting method.

Intermittent pneumatic compression (IPC) therapy has been adopted in prevention and treatment of ischemic-related peripheral vascular diseases. The aim of this study is to provide an approach to personalize the compression strategy of IPC therapy for maximizing foot skin blood flow. In this study, we presented a method to predict the optimized compression mode (OCM) for each subject based on biomechanical features extracted from experimental data tested with multiple IPC modes. First, to demonstrate the blood flow enhancing effect by applying the personalized OCM, four IPC modes of different frequency settings were tested on a total of 24 subjects. The frequency settings were adjusted by deflating-waiting time, which was defined as the total time length from the start of cuff deflation to the start of next compression. The foot skin blood perfusion and IPC air cuff pressure were monitored during the experiments. The personalized OCM was defined as the certain IPC mode that has the highest blood perfusion augmentation (BPA). Compared with the rest stage blood perfusion, the personalized OCM settings resulted in >50% of augmentation for 75% of healthy subjects (maximum augmentation at 244%) and >20% augmentation for 75% of patients with diabetes (maximum augmentation at 180%). Second, for predicting the OCM, we establish a random forest model based on the features extracted from the experimental data. The binary classification resulted in acceptable prediction performance (AUC > 0.7). This study might inspire new IPC strategies for improving foot microcirculation.

Sodium butyrate facilitates CRHR2 expression to alleviate HPA axis hyperactivity in autism-like rats induced by prenatal lipopolysaccharides through histone deacetylase inhibition.

Short-chain fatty acids (SCFAs, especially butyric acid) have been demonstrated to play a promising role in the development of autism spectrum disorders (ASD). Recently, the hypothalamic-pituitary-adrenal (HPA) axis is also suggested to increase the risk of ASD. However, the mechanism underlying SCFAs and HPA axis in ASD development remains unknown. Here, we show that children with ASD exhibited lower SCFA concentrations and higher cortisol levels, which were recaptured in prenatal lipopolysaccharide (LPS)-exposed rat model of ASD. These offspring also showed decreased SCFA-producing bacteria and histone acetylation activity as well as impaired corticotropin-releasing hormone receptor 2 (CRHR2) expression. Sodium butyrate (NaB), which can act as histone deacetylases inhibitors, significantly increased histone acetylation at the CRHR2 promoter in vitro and normalized the corticosterone as well as CRHR2 expression level in vivo. Behavioral assays indicated ameliorative effects of NaB on anxiety and social deficit in LPS-exposed offspring. Our results imply that NaB treatment can improve ASD-like symptoms via epigenetic regulation of the HPA axis in offspring; thus, it may provide new insight into the SCFA treatment of neurodevelopmental disorders like ASD. IMPORTANCE Growing evidence suggests that microbiota can affect brain function and behavior through the "microbiome-gut-brain'' axis, but its mechanism remains poorly understood. Here, we show that both children with autism and LPS-exposed rat model of autism exhibited lower SCFA concentrations and overactivation of HPA axis. SCFA-producing bacteria, Lactobacillus, might be the key differential microbiota between the control and LPS-exposed offspring. Interestingly, NaB treatment contributed to the regulation of HPA axis (such as corticosterone as well as CRHR2) and improvement of anxiety and social deficit behaviors in LPS-exposed offspring. The potential underlying mechanism of the ameliorative effect of NaB may be mediated via increasing histone acetylation to the CRHR2 promoter. These results enhance our understanding of the relationship between the SCFAs and the HPA axis in the development of ASD. And gut microbiota-derived SCFAs may serve as a potential therapeutic agent to neurodevelopmental disorders like ASD.

Antimicrobial activity of gamma-poly (glutamic acid), a preservative coating for cherries.

We investigated the minimum inhibitory concentration (MIC), antibacterial activity, and preservation ability of four molar masses of γ-polyglutamic acid (PGA) against Escherichia coli, Bacillus subtilis, and yeast. The antibacterial mechanism was determined based on the cell structure, membrane permeability, and microscopic morphology of the microorganisms. We then measured the weight loss, decay rate, total acid, catalase activity, peroxidase activity, and malondialdehyde content toward the possible use of PGA as a preservative coating for cherries. When the molar mass was greater than 700 kDa, the MIC for Escherichia coli and Bacillus subtilis was less than 2.5 mg/mL. The mechanism of action of the four molar masses of PGA was different with respect to the three microbial species, but a higher molar mass of PGA corresponded to stronger inhibition against the microbes. PGA of 2000 kDa molar mass damaged the microbial cellular structure, resulting in excretion of alkaline phosphatase, but PGA of 1.5 kDa molar mass affected the membrane permeability and the amount of soluble sugar. Scanning electron microscopy indicated the inhibitory effect of PGA. The antibacterial mechanism of PGA was related to the molar mass of PGA and the microbial membrane structure. Compared with the control, a PGA coating effectively inhibit the spoilage rate, delay the ripening, and prolong the shelf life of cherries.

Multiple blood flow surges during intermittent pneumatic compression: The origins and their implications.

Intermittent pneumatic compression (IPC) therapy has been used to enhance peripheral blood flow for prevention and rehabilitation of ischemic-related vascular diseases. A novel phenomenon has been reported that multiple blood flow surges appeared in the skin blood flow signal during each compression, but its mechanism has not been fully revealed. This study aimed to gain insights into the origins of these blood flow surges through experiment and biomechanical modeling methods. Foot skin blood flow (SBF) signals of 13 healthy adults (23.8 ± 0.5 yr old, 7 males) and air cuff pressure signals were recorded during IPC. Lumped parameter modeling and wavelet analysis were adopted to investigate the multiple blood flow surges (named as Peak1, Peak2 and Peak3). The results of the simulated Peak1 and Peak2 were in good agreements with the experiment results, suggesting that IPC could enhance foot SBF not only by deflation, but also by inflation. Statistical analysis demonstrated that high frequency compression with more frequent occurrence of Peak1 and Peak2 lead to significantly higher (Friedman test, p < 0.001) time-averaged SBF enhancement than the traditional mode. In addition, wavelet analysis showed that the major frequency component of the Peak3 (0.059 Hz) was within the range of the vascular myogenic activity, suggesting a vascular regulation process triggered by intravascular pressure changes. Our study provide new insights into the mechanism of how IPC enhance foot SBF.

Variations of human cerebral and ocular blood flow during exposure to multi-axial accelerations : A mathematical modeling study.

Human hemodynamic responses during exposure to multi-axial acceleration was a relatively new topic in the fields of acceleration physiology. This study aimed to focus on these responses, especially variations of blood perfusion to brain and eyes, through mathematical modeling. A mathematical model was established using lumped parameter methods, containing compartments of four heart chambers, systemic arteries and veins, circulation of typical systemic organs, and some compartments for pulmonary circulation, together with autonomic regulation considered. This model was firstly validated by using experimental data from experiment of posture change and centrifuge tests of +Gz accelerations, and then applied to analyze human hemodynamic responses to typical multi-axial accelerations. Validation results demonstrated the mathematical model could generate reasonable responses of human cardiovascular system during posture change and exposure to +Gz accelerations. Simulation results of hemodynamic responses to multi-axial accelerations depicted Gy induced significant differences of blood flow to the left and right eyes. And some contour maps were generated based on these results, which provided a quick way to estimate blood flow variations in brain and eyes during exposure to different accelerations. Graphical Abstract This study aimed to focus on variations of blood perfusion to brain and eyes during exposure to typical multi-axial accelerations through mathematical modeling. This model was firstly validated by using experimental data from experiment of posture change and centrifuge tests of +Gz accelerations, and then applied to analyze human hemodynamic responses to typical multi-axial accelerations. Simulation results of hemodynamic responses to multi-axial accelerations depicted Gy induced significant differences of blood flow to the left and right eyes. And contour maps that generated based on these results provided a quick way to estimate blood flow variations in brain and eyes during exposure to different accelerations.