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Chronic constipation is a functional gastrointestinal disease that is detrimental to the quality of patient life. Cassia obtusifolia L. (CO) and Foeniculum vulgare M. (FV) are commonly used as medicinal foods in many countries. We aimed to examine the laxative effect and their underlying mechanism of CO and FV mixture on loperamide (lop)-induced constipated rats. To determine the laxative effects of these compounds, Sprague-Dawley rats were divided into six groups: the control, lop-induced constipated (2mg/kg), and three doses (100, 300, and 500mg/kg) of CO and FV mixture-, and Bisacodyl (bis, 3.3mg/kg)-treated groups. The mixture of CO and FV and bis were orally administered once a day for 4 weeks. For induction of constipation, the lop were treated with a dose of 2 mg/kg twice a day on the 3rd week after treatments of CO and FV extracts and bis. The results were revealed that the CO and FV mixture has the laxative effects more than those in CO and FV-alone treatments on constipated rats by determining the stool parameters, including stool number and weight. Indeed, stool parameters, such as, stool number, weight, and water contents and colonic peristalsis from the intestinal transit length and ratio were dramatically improved by CO and FV mixture treatment. Histological study also revealed that CO and FV mixture enhanced the thicknesses of mucosa and muscular layers of the colon in constipated rats. For their underlying mechanism, the mRNAs and proteins expression of muscarinic acetylcholine receptors (mAchR) M2 and M3 and their downstream signaling were preserved by CO and FV mixture treatment in constipated rats. Therefore, this study suggests that treatment with CO and FV mixture has beneficial effects against constipation. We further suggest that CO and FV mixture may be utilized as an alternative therapeutic strategy for constipation. [ABSTRACT FROM AUTHOR]

The brain is highly energy consuming, therefore is under strong selective pressure to achieve cost-efficiency in both cortical connectivities and activities. However, cost-efficiency as a design principle for cortical activities has been rarely studied. Especially it is not clear how cost-efficiency is related to ubiquitously observed multi-scale properties: irregular firing, oscillations and neuronal avalanches. Here we demonstrate that these prominent properties can be simultaneously observed in a generic, biologically plausible neural circuit model that captures excitation-inhibition balance and realistic dynamics of synaptic conductance. Their co-emergence achieves minimal energy cost as well as maximal energy efficiency on information capacity, when neuronal firing are coordinated and shaped by moderate synchrony to reduce otherwise redundant spikes, and the dynamical clusterings are maintained in the form of neuronal avalanches. Such cost-efficient neural dynamics can be employed as a foundation for further efficient information processing under energy constraint. [ABSTRACT FROM AUTHOR]

The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet. [ABSTRACT FROM AUTHOR]

Although hemodynamic influence of the subprosthetic tissue, termed as pannus, may contribute to prosthetic aortic valve dysfunction, the relationship between pannus extent and hemodynamics in the prosthetic valve has rarely been reported. We investigated the fluid dynamics of pannus formation using in vitro experiments with particle image velocimetry. Subvalvular pannus formation caused substantial changes in prosthetic valve transvalvular peak velocity, transvalvular pressure gradient (TPG) and opening angle. Maximum flow velocity and corresponding TPG were mostly affected by pannus width. When the pannus width was 25% of the valve diameter, pannus formation elevated TPG to >2.5 times higher than that without pannus formation. Opening dysfunction was observed only for a pannus involvement angle of 360°. Although circumferential pannus with an involvement angle of 360° decreased the opening angle of the valve from approximately 82° to 58°, eccentric pannus with an involvement angle of 180° did not induce valve opening dysfunction. The pannus involvement angle largely influenced the velocity flow field at the aortic sinus and corresponding hemodynamic indices, including wall shear stress, principal shear stress and viscous energy loss distributions. Substantial discrepancy between the velocity-based TPG estimation and direct pressure measurements was observed for prosthetic valve flow with pannus formation. [ABSTRACT FROM AUTHOR]

Background: Rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. The rapid fluorescent focus inhibition test (RFFIT) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. Here, we report the development of a new monoclonal antibody (mAb) designed to react specifically with Rabies virus (RABV) phosphoprotein (P protein), and the evaluation of its applicability to the RFFIT and its effectiveness as a diagnostic reagent for human rabies. Methodology/principal findings: The mAb KGH P 16B8 was produced to target the P protein of the Korean KGH RABV strain. An indirect immunofluorescence assay (IFA) was conducted to detect various strains of RABV in various cell lines. Alexa-conjugated KGH P 16B8 (16B8-Alexa) was developed for the RFFIT. The IFA test could detect RABV up to a 1:2,500 dilution, with a detection limit comparable to that of a commercial diagnostic reagent. The sensitivity, specificity, positive predictive value, and negative predictive value of the RFFIT using 16B8-Alexa in 414 clinical specimens were 98.67%, 99.47%, 99.55%, and 98.42%, respectively. The results of the RFFIT with 16B8-Alexa were strongly correlated with those obtained using an existing commercial diagnostic reagent (r = 0.995, p<0.001). Conclusions/significance: The mAb developed in this study shows high sensitivity and specificity, confirming its clinical utility with the RFFIT to measure the rabies neutralizing antibody titer and establish a diagnosis in human. Thus, 16B8-Alexa is expected to serve as an alternative diagnostic reagent that is widely accessible, with potentially broad applications beyond those of the RFFIT in Korea. Further studies with 16B8-Alexa should provide insight into the immunological mechanism of the P protein of Korean RABV. [ABSTRACT FROM AUTHOR]

Intestinal inflammation and mucosal damage in Crohn’s disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn’s disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8–8.0]), the Kaplan–Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245–2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003–2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Streptococcus suis serotype 2 (SS2) is a major porcine and human pathogen which causes arthritis, meningitis, and septicemia. Streptococcus suis nuclease A (SsnA) is a recently discovered deoxyribonuclease (DNase), which has been demonstrated to contribute to escape killing in neutrophil extracellular traps (NETs). To further determine the effects of ssnA on virulence, the ssnA deletion mutant (ΔssnA) and its complemented strain (C-ΔssnA) were constructed. The ability of ΔssnA mutant to interact with human laryngeal epithelial cell (Hep-2) was evaluated and it exhibited dramatically decreased ability to adhere to and invade Hep-2 cells. This mutation was found to exhibit significant attenuation of virulence when evaluated in CD1 mice, suggesting ssnA plays a critical role in the pathogenesis of SS2. Finally, we found that immunization with the ΔssnA mutant triggered both antibody responses and cell-mediated immunity, and conferred 80% protection against virulent SS2 challenge in mice. Taken together, our results suggest that ΔssnA represents an attractive candidate for designing an attenuated live vaccine against SS2. [ABSTRACT FROM AUTHOR]

Background: Although the measurement of turbulence kinetic energy (TKE) by using magnetic resonance imaging (MRI) has been introduced as an alternative index for quantifying energy loss through the cardiac valve, experimental verification and clinical application of this parameter are still required. Objectives: The goal of this study is to verify MRI measurements of TKE by using a phantom stenosis with particle image velocimetry (PIV) as the reference standard. In addition, the feasibility of measuring TKE with MRI is explored. Methods: MRI measurements of TKE through a phantom stenosis was performed by using clinical 3T MRI scanner. The MRI measurements were verified experimentally by using PIV as the reference standard. In vivo application of MRI-driven TKE was explored in seven patients with aortic valve disease and one healthy volunteer. Transvalvular gradients measured by MRI and echocardiography were compared. Results: MRI and PIV measurements of TKE are consistent for turbulent flow (0.666 < R2 < 0.738) with a mean difference of −11.13 J/m3 (SD = 4.34 J/m3). Results of MRI and PIV measurements differ by 2.76 ± 0.82 cm/s (velocity) and −11.13 ± 4.34 J/m3 (TKE) for turbulent flow (Re > 400). The turbulence pressure drop correlates strongly with total TKE (R2 = 0.986). However, in vivo measurements of TKE are not consistent with the transvalvular pressure gradient estimated by echocardiography. Conclusions: These results suggest that TKE measurement via MRI may provide a potential benefit as an energy-loss index to characterize blood flow through the aortic valve. However, further clinical studies are necessary to reach definitive conclusions regarding this technique. [ABSTRACT FROM AUTHOR]

This paper reports on studies of the effect of temperature step-change (between a cool and a neutral environment) on human thermal sensation and skin temperature. Experiments with three temperature conditions were carried out in a climate chamber during the period in winter. Twelve subjects participated in the experiments simulating moving inside and outside of rooms or cabins with air conditioning. Skin temperatures and thermal sensation were recorded. Results showed overshoot and asymmetry of TSV due to the step-change. Skin temperature changed immediately when subjects entered a new environment. When moving into a neutral environment from cool, dynamic thermal sensation was in the thermal comfort zone and overshoot was not obvious. Air-conditioning in a transitional area should be considered to limit temperature difference to not more than 5°C to decrease the unacceptability of temperature step-change. The linear relationship between thermal sensation and skin temperature or gradient of skin temperature does not apply in a step-change environment. There is a significant linear correlation between TSV and Qloss in the transient environment. Heat loss from the human skin surface can be used to predict dynamic thermal sensation instead of the heat transfer of the whole human body. [ABSTRACT FROM AUTHOR]