Subtle changes in the flavour and texture of a drink enhance expectations of satiety

Background: The consumption of liquid calories has been implicated in the development of obesity and weight gain. Energy-containing drinks are often reported to have a weak satiety value: one explanation for this is that because of their fluid texture they are not expected to have much nutritional value. It is important to consider what features of these drinks can be manipulated to enhance their expected satiety value. Two studies investigated the perception of subtle changes in a drink’s viscosity, and the extent to which thick texture and creamy flavour contribute to the generation of satiety expectations. Participants in the first study rated the sensory characteristics of 16 fruit yogurt drinks of increasing viscosity. In study two, a new set of participants evaluated eight versions of the fruit yogurt drink, which varied in thick texture, creamy flavour and energy content, for sensory and hedonic characteristics and satiety expectations. Results: In study one, participants were able to perceive small changes in drink viscosity that were strongly related to the actual viscosity of the drinks. In study two, the thick versions of the drink were expected to be more filling and have a greater expected satiety value, independent of the drink’s actual energy content. A creamy flavour enhanced the extent to which the drink was expected to be filling, but did not affect its expected satiety. Conclusions: These results indicate that subtle manipulations of texture and creamy flavour can increase expectations that a fruit yogurt drink will be filling and suppress hunger, irrespective of the drink’s energy content. A thicker texture enhanced expectations of satiety to a greater extent than a creamier flavour, and may be one way to improve the anticipated satiating value of energy-containing beverages

Chemoenzymatic Synthesis of Glycosylated Macrolactam Analogues of the Macrolide Antibiotic YC‐17

YC‐17 is a 12‐membered ring macrolide antibiotic produced from Streptomyces venezuelae ATCC 15439 and is composed of the polyketide macrolactone 10‐deoxymethynolide appended with D‐desosamine. In order to develop structurally diverse macrolactam analogues of YC‐17 with improved therapeutic potential, a combined approach involving chemical synthesis and engineered cell‐based biotransformation was employed. Eight new antibacterial macrolactam analogues of YC‐17 were generated by supplying a novel chemically synthesized macrolactam aglycone to S. venezuelae mutants harboring plasmids capable of synthesizing several unnatural sugars for subsequent glycosylation. Some YC‐17 macrolactam analogues were active against erythromycin‐resistant bacterial pathogens and displayed improved metabolic stability in vitro. The enhanced therapeutic potential demonstrated by these glycosylated macrolactam analogues reveals the unique potential of chemoenzymatic synthesis in antibiotic drug discovery and development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/1/adsc_201500250_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113147/2/2697_ftp.pd

Smoking Cessation Quitlines in Europe: Matching Services to Callers' Characteristics

<p>Abstract</p> <p>Background</p> <p>Telephone quitlines offer a wide range of services to callers, including advice and counsel, and information on pharmacotherapy for smoking cessation. But, little is known about what specific quitline services are offered to smokers and whether these services are appropriately matched to characteristics of smokers. This study examines how quitline services are matched to callers' level of addiction, educational level, stage-of-change with quitting, and whether they are referred by a doctor or other health professional.</p> <p>Methods</p> <p>Between February 2005 and April 2006, 3,585 callers to seven European quitlines responded to our survey. During the course of and immediately after the call, quitline counsellors collected descriptive data on callers' characteristics and the services they used. We then conducted four logistic regression analyses to examine the relationship between quitline services and the four caller characteristics.</p> <p>Results</p> <p>Forty three percent of all callers received information on pharmacotherapy - most often nicotine patches and nicotine gum - from the counsellor. As we predicted, these callers were the heavy smokers. There was a direct correlation between the length of the conversations between the counsellor and the educational level of the smoker: the lower the education of the smoker, the shorter the call. However, we found no significant association between any other type of service and the educational level of caller. We also found a correlation between the smoker's stage of quitting and the type of advice a counsellor gives. Smokers in the action stage of quitting were more likely to receive advice (in two quitlines) or counselling (in two quitlines) than those in the preparation stage, who were less likely to be referred (in three quitlines). Very few of the total number of calls (10.7%) were from referrals by health professionals. Referred callers were more likely to receive counselling, but this was found only in four of seven quitlines.</p> <p>Conclusion</p> <p>Most of the services quitlines offer to smokers favour heavy smokers and those at a more advanced stage of cessation, but not based on their educational level. Thus, we recommend that European quitlines extend and tailor their services to include less-educated smokers.</p

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

A Decline in Renal Function is Associated With Loss of Bone Mass in Korean Postmenopausal Women With Mild Renal Dysfunction

This study was conducted to assess the relationship between estimated glomerular filtration rate (eGFR) and bone mineral density (BMD) in Korean postmenopausal women with mild renal dysfunction. A total of 328 postmenopausal women who underwent BMD measurement during health check-up was investigated. BMD was measured in lumbar spine (L1-L4), femoral neck, total proximal femur and femoral trochanteric areas by dual energy radiography absorptiometry and renal function was estimated by eGFR using Cockcroft-Gault equation. Of the 328 subjects, 317 (96.6%) had an eGFR ≥60 mL/min/1.73 m2. By using simple linear regression analysis, age, height, weight and eGFR were significantly associated with BMD for the 4 aforementioned anatomic sites, while serum levels of creatinine and blood urea nitrogen did not influence BMD. When multiple regression analyses were applied, age and body weight still had significant associations with BMD at 4 different anatomic sites (P < 0.001). A significant association of eGFR with BMD remained in the lumbar spine, femoral neck and proximal total femur (P < 0.05) but not in the trochanteric area (P = 0.300). Our study suggests that a decline of renal function is associated with lower BMD in the lumbar spine, femoral neck and total proximal femur areas in Korean menopausal women with mild renal dysfunction

Mutation of pescadillo Disrupts Oligodendrocyte Formation in Zebrafish

Background: In vertebrates, the myelin sheath is essential for efficient propagation of action potentials along the axon shaft. Oligodendrocytes are the cells of the central nervous system that create myelin sheaths. During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system. This study aimed to investigate mechanisms that regulate oligodendrocyte progenitor cell formation. Methodology/Principal Findings: By conducting a mutagenesis screen in transgenic zebrafish, we identified a mutation, designated vu166, by an apparent reduction in the number of oligodendrocyte progenitor cells in the dorsal spinal cord. We subsequently determined that vu166 is an allele of pescadillo, a gene known to play a role in ribosome biogenesis and cell proliferation. We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression. Conclusions/Significance: Our data provide evidence that neural precursors require pes function to progress through th

Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis

<p>Abstract</p> <p>Background</p> <p>Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography and benefit of pharmacological treatment is unclear. Although prophylactic use of corticosteroid for reduction of pancreatic injury after ERCP has been evaluated, discrepancy about beneficial effect of corticosteroid on pancreatic injury still exists. The aim of current study is to evaluate effectiveness and safety of corticosteroid in prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP).</p> <p>Methods</p> <p>We employed the method recommended by the Cochrane Collaboration to perform a meta-analysis of seven randomized controlled trials (RCTs) of corticosteroid in prevention of post-ERCP pancreatitis (PEP) around the world.</p> <p>Results</p> <p>Most of the seven RCTs were of high quality. When the RCTs were analyzed, odds ratios (OR) for corticosteroid were 1.13 [95% CI (0.89~1.44), p = 0.32] for PEP, 1.61 [95% CI (0.74~3.52), p = 0.23] for severe PEP, 0.92 [95% CI (0.57~1.48), p = 0.73] for post-ERCP hyperamylasemia respectively. The results indicated that there were no beneficial effects of corticosteroid on acute pancreatitis and hyperamylasemia. No evidence of publication bias was found.</p> <p>Conclusion</p> <p>Corticosteroids cannot prevent pancreatic injury after ERCP. Therefore, their use in the prophylaxis of PEP is not recommended.</p

Simply imagining sunshine, lollipops and rainbows will not budge the bias: The role of ambiguity in interpretive bias modification

Imagery-based interpretive bias modification (CBM-I) involves repeatedly imagining scenarios that are initially ambiguous before being resolved as either positive or negative in the last word/s. While the presence of such ambiguity is assumed to be important to achieve change in selective interpretation, it is also possible that the act of repeatedly imagining positive or negative events could produce such change in the absence of ambiguity. The present study sought to examine whether the ambiguity in imagery-based CBM-I is necessary to elicit change in interpretive bias, or, if the emotional content of the imagined scenarios is sufficient to produce such change. An imagery-based CBM-I task was delivered to participants in one of four conditions, where the valence of imagined scenarios were either positive or negative, and the ambiguity of the scenario was either present (until the last word/s) or the ambiguity was absent (emotional valence was evident from the start). Results indicate that only those who received scenarios in which the ambiguity was present acquired an interpretive bias consistent with the emotional valence of the scenarios, suggesting that the act of imagining positive or negative events will only influence patterns of interpretation when the emotional ambiguity is a consistent feature