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  • Gentry posted an update 7 months, 2 weeks ago

    The formation of reactive metabolites (RMs) is a problem in drug development that sometimes results in severe hepatotoxicity. PFTα As detecting RMs themselves is difficult, a covalent binding assay using expensive radiolabelled tracers is usually performed for candidate selection. This study aimed to provide a practical approach toward the risk assessment of hepatotoxicity induced by covalent binding before candidate selection. We focused on flutamide because it contains a trifluoromethyl group that shows a strong singlet peak by 19F nuclear magnetic resonance (NMR) spectrometry. The covalent binding of flutamide was evaluated using quantitative NMR and its risk for hepatotoxicity was assessed by estimating the RM burden, an index that reflects the body burden associated with RM exposure by determining the extent of covalent binding, clinical dose and in vivo clearance. The extent of covalent binding and RM burden was 296 pmol/mg/h and 37.9 mg/day, respectively. Flutamide was categorised as high risk with an RM burden >10 mg/day consistent with its clinical hepatotoxicity. These results indicate that a combination of covalent binding assay using 19F-NMR and RM burden is useful for the risk assessment of RMs without using radiolabelled compounds.This study aimed at purification of phycocyanin (PC) from Phormidium tergestinum using an aqueous two-phase system (ATPS) comprised of polyethylene glycol (PEG) and salts. The partitioning efficiency of PC in ATPS and the effect of phase composition, pH, crude loading, and neutral salts on purification factor and yield were investigated. Results showed that PC was selectively partitioned toward bottom phase of the system containing potassium phosphate. Under optimum conditions of 20% (w/w) PEG 4000, 10% (w/w) potassium phosphate, 20% (v/v) crude load at pH 7, with addition of 0.5% (w/w) NaCl, PC from P. tergestinum was partially purified up to 5.34-fold with a yield of 87.8%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the molecular weight of PC was ∼19 kDa. Results from this study demonstrated ATPS could be used as a potential approach for the purification of PC from P. tergestinum.Technology can enable efficient, effective, and independent performance of daily occupations and enhance social and leisure participation. This paper describes the findings of a qualitative study exploring iPad use during daily activities among adults with low vision. Five women who previously participated in a group iPad intervention participated in the study. Thematic analysis revealed 5 main themes integration of the iPad into daily routine, benefits and barriers of the iPad, psychosocial factors, preferences regarding iPad use, and group instruction in individual iPad use. Group instruction may be a viable intervention option in low vision rehabilitation to improve occupational participation.

    Early detection of inner ear cell damage can reduce the chances of permanent damage to hearing ability. However, current inner ear cell damage detection methods can detect damage only after the patient has lost hearing ability. MicroRNA expression levels in circulating systems are affected in diseases or conditions arising from the distant lesions. Therefore, detection of circulating microRNA expression levels could be one of the best ways to obtain information on inaccessible lesion sites.

    This study aims to establish a method for monitoring idiopathic sudden sensorineural hearing loss (ISSNHL) by analyzing circulating microRNA expression levels. 21 ISSNHL patients and 24 healthy controls were enrolled.

    Real-time quantitative polymerase chain reaction was performed for detecting expression levels of circulating microRNAs.

    Among eight circulating microRNAs, expression levels of five circulating microRNAs significantly differed between ISSNHL patients and healthy controls. circulating microRNA expression levels correlates with treatment outcomes and hearing ability.

    Using methods combining the evaluation of miR-183, miR-210, miR-18b, and miR-23a cut-off values identified in ISSNHL patients and healthy controls during receiver operating characteristic curve analysis, sensitivity and specificity of 80.95% (17/21) and 87.50% (21/24) were obtained, respectively.

    Using methods combining the evaluation of miR-183, miR-210, miR-18b, and miR-23a cut-off values identified in ISSNHL patients and healthy controls during receiver operating characteristic curve analysis, sensitivity and specificity of 80.95% (17/21) and 87.50% (21/24) were obtained, respectively.Moist exposed burn ointment (MEBO) is an oil-based herbal paste, purported to be efficacious in managing burn wounds and more commonly used in Asia and the Middle East. A PRISMA-compliant systematic review was performed to analyse the evidence for the use of MEBO on burn wounds. Wound healing rate was the primary outcome of interest. PubMed-listed randomised controlled trials (RCTs) comparing the efficacy of MEBO with placebo, standard care or other therapies in the treatment of partial thickness burns in adults and children were eligible for inclusion (November 2019). Six RCTs were eligible. The majority of trials comparing wound healing between MEBO and SSD favoured MEBO (two of three). There may be improved healing in MEBO-treated wounds vs. those treated with povidone-iodine + bepanthenol cream. There was no difference between MEBO and Acquacel Ag, but Helix Aspersa had faster healing rates than MEBO. However, all evidence was from moderately to poorly reported trials with a high risk of bias, thereby limiting the strength of this evidence. In conclusion, the evidence for MEBO in English-language literature was poor and inconsistent with respect to wound healing rate and analgesis compared to 1% SSD, Acquacel Ag, Helix aspersa cream and povidone-iodine + bepanthenol cream. Blinded RCTs comparing MEBO to both placebo and other common topical treatments may further improve the confidence in concluding their analysis. There is some evidence that MEBO is as safe as its comparators as shown by the low complication rate.Rumen development is critical for the development of early lambs. This work aims to evaluate the effects of abrupt weaning at day 21 on rumen fermentation, histomorphological traits and the ruminal microbiota compared with continuous suckling. Twelve pairs of artificially reared full-sib neonatal male Hu lambs were allocated to two groups, one of which was weaned at day 21 (EW group) and the other which was not weaned (CON group). At day 26 and day 49, six lambs from each group were randomly selected and sacrificed to collect ruminal contents and rumen tissue samples. Results showed that weaning influenced the fermentation parameters in the rumen, and altered the microbial community composition on day 49 (p  less then  0.05). Several genera were associated with rumen fermentation parameters (p  less then  0.05). Volatile fatty acid (VFA) concentration is the key parameter impacting microbiota composition. Weaning influenced the expression of genes associated with VFA metabolism and regulation of cell proliferation (p  less then  0.

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