Bile acids (BAs) as important endogenous ligands can activate farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) signaling to regulate glycolipid metabolism. In this study, a simple, reliable and sensitive analysis method for simultaneous determination of four BAs from rat feces based on high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. Chromatographic analysis was performed with the mobile phases of acetonitrile and 0.2% formic acid. All the standard curves exhibited good linearity (R2 ≥ 0.99).  https://www.selleckchem.com/  The relative standard deviations of precision, stability and repeatability varied from 1.27 to 3.96%, 2.20 to 3.89% and 3.00 to 4.31%, respectively. The validated method was successfully applied to investigate the variation of four BAs in feces from T2DM rats after oral administration of Sanhuang Xiexin Tang (SXT). Data showed that SXT could remarkably increase the contents of conjunct BAs and decrease the contents of free BAs, which might contribute to ameliorate the symptoms of T2DM rats.A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).Medical nutrition therapy (MNT) is the bedrock for the management of gestational diabetes mellitus (GDM). Several different types of dietary approaches are used globally, and there is no consensus among the various professional groups as to what constitutes an ideal approach. The conventional approach of limiting carbohydrates at the cost of increasing energy from the fat source may not be most optimal. Instead, allowing higher levels of complex, low-to-medium glycaemic index carbohydrates and adequate fibre through higher consumption of vegetables and fruits seems more beneficial. No particular diet or dietary protocol is superior to another as shown in several comparative studies. However, in each of these studies, one thing was common - the intervention arm included more intensive diet counselling and more frequent visits to the dieticians. For MNT to work, it is imperative that diet advice and nutrition counselling is provided by a dietician, which is easy to understand and use and includes healthy food options, cooking methods, and practical guidance that empower and motivate to make changes towards a healthy eating pattern. Various simple tools to achieve these objectives are available, and in the absence of qualified dieticians, they can be used to train other health care professionals to provide nutrition counselling to women with GDM. Given the impact of GDM on the future health of the mother and offspring, dietary and lifestyle behaviour changes during pregnancy in women with GDM are not only relevant for immediate pregnancy outcomes, but continued adherence is also important for future health.
  The purpose of this study was to establish and characterize age- and gender-specific normative data of the singing voice using the voice range profile for clinical diagnostics. Furthermore, associations between the singing voice and the socioeconomic status were examined.
 
  Singing voice profiles of 1,578 mostly untrained children aged between 7.0 and 16.11 years were analyzed. Participants had to reproduce sung tones at defined pitches, resulting in maximum and minimum fundamental frequency and sound pressure level (SPL). In addition, maximum phonation time (MPT) was measured. Percentile curves of frequency, SPL and MPT were estimated. To examine the associations of socioeconomic status, multivariate analyses adjusted for age and sex were performed.
 
  In boys, the mean of the highest frequency was 750.9 Hz and lowered to 397.1 Hz with increasing age. Similarly, the minimum frequency was 194.4 Hz and lowered to 91.9 Hz. In girls, the mean maximum frequency decreased from 754.9 to 725.3 Hz. The mean minimum plied to distinguish between normal and pathological singing voice.
  Current guidelines recommend transthoracic echocardiography (TTE) and ambulatory rhythm monitoring following ischemic stroke or transient ischemic attack (TIA) of undetermined cause for identifying cardioembolic sources (CES). Due to ongoing controversies about this routine strategy, we evaluated its yield in a real-world setting.
 
  In a tertiary medical center, we retrospectively evaluated consecutive patients with ischemic stroke or TIA of undetermined cause, who (after standard work-up) underwent TTE, ambulatory rhythm monitoring, or both. CES were classified as major if probably related to ischemic events and warranting a change of therapy.
 
  Between January 2014 and December 2017, 674 patients had ischemic stroke or TIA of undetermined cause. Of all 484 patients (71.8%) who underwent TTE, 9 (1.9%) had a major CES. However, 7 of them had already been identified for cardiac evaluation due to new major electrocardiographic abnormalities or cardiac symptoms. Thus, only 2 patients (0.4%) truly benefitted from unselected TTE screening.