Predictors of programme adherence and weight loss in women in an obesity programme using meal replacements

Objective: To explore predictors of programme adherence and weight loss in patients participating in a weight management programme using meal replacements (MR).Design: One hundred and fifty healthy obese women, age 48.5 years (s.d. = 8.3); weight, 97.6 kg (13.4); body mass index (BMI) 36.5 (3.7), participated in a longitudinal study with a 16-week acute weight loss phase (Phase 1) followed by 1 year of a trial of weight-loss maintenance (Phase 2). Energy intake during Phase 1 totaled 900 kcal (3.7 MJ) a day from a diet including two MR. Energy intake during Phase 2 consisted of either MR or a low-fat diet with a calculated energy deficit of 600 kcal/day (2.5 MJ).Methods: Weight, height and waist circumference were measured and body composition assessed by air plethysmography (Bodpod). Glucose and insulin were measured by standard immunoassays and insulin sensitivity assessed by homeostatic model assessment.Results: At the end of 16 weeks, 114 subjects (76%) completed Phase 1 and achieved a mean weight loss of 8.95 kg (3.38). Adherence to Phase 1 was predicted by weight loss over the first 2 weeks (p < 0.001). Weight loss during Phase 1 was predicted by initial weight and initial systolic blood pressure. Adherence to Phase 2 was not predicted by physiological measures. Weight loss maintenance in Phase 2 (not gaining more than 3% of the weight at start of phase 2) was predicted by cholesterol and triglyceride measured at the start of Phase 2 but otherwise was not predicted by the physiological measures. Initial insulin sensitivity did not predict weight loss in either phase.Conclusion: Participants whose weight loss over the first 2 weeks falls in the bottom third may need additional intervention if they are to continue in this type of programme. A battery of physiological measures at entry to a MR weight loss and maintenance programme explains only a very small proportion of the variation in weight loss

Trends in Ages at Key Reproductive Transitions in the United States, 1951–2010

AbstractBackgroundKey sexual and reproductive health milestones typically mark changing life stages with different fertility intentions and family planning needs. Knowing the typical ages at such events contributes to our understanding of changes in family formation and transition to adulthood and helps inform needs for reproductive health services.MethodsWe used data from the 1982–2010 National Surveys of Family Growth and the 1995 National Survey of Adolescent Males and event history methods to examine trends over time for women and men in the median ages at several reproductive and demographic events.FindingsWomen's reports indicate that age at menarche has changed little since 1951. Women's and men's median ages at first sex declined through the 1978 birth cohort, but increased slightly since then, to 17.8 years for women and 18.1 for men. The interval from first sex to first contraceptive use has narrowed, although Hispanic women have a longer interval. Age at first union (defined as the earlier of first marriage or first cohabiting relationship) has remained relatively stable, but the time between median age at first sex and median age at first birth has increased to 9.2 years for women and 11.4 for men. For some women and men born in the late 1970s, median age at first birth was earlier than median age at first marriage for the first time in at least the past several decades.ConclusionThe large majority of the reproductive years are spent sexually active. Thus, women have a lengthy period during which they require effective methods. In particular, the period between first sex and first childbearing has lengthened, but long-acting method use, although increasing, has not kept up with this shift. Moving the contraceptive method mix toward underutilized but highly effective contraceptive methods has the potential to reduce the unintended pregnancy rate

Rimonabant improves cardiometabolic risk factors in overweight/obese patients with poorly controlled type 2 diabetes (HbA(1c)>= 8%) on monotherapy with metformin or sulfonylureas

peer reviewe

Robotics and Dynamic Image Analysis for Studies of Gene Expression in Plant Tissues

Gene expression in plant tissues is typically studied by destructive extraction of compounds from plant tissues for in vitro analyses. The methods presented here utilize the green fluorescent protein (gfp) gene for continual monitoring of gene expression in the same pieces of tissues, over time. The gfp gene was placed under regulatory control of different promoters and introduced into lima bean cotyledonary tissues via particle bombardment. Cotyledons were then placed on a robotic image collection system, which consisted of a fluorescence dissecting microscope with a digital camera and a 2-dimensional robotics platform custom-designed to allow secure attachment of culture dishes. Images were collected from cotyledonary tissues every hour for 100 hours to generate expression profiles for each promoter. Each collected series of 100 images was first subjected to manual image alignment using ImageReady to make certain that GFP-expressing foci were consistently retained within selected fields of analysis. Specific regions of the series measuring 300 x 400 pixels, were then selected for further analysis to provide GFP Intensity measurements using ImageJ software. Batch images were separated into the red, green and blue channels and GFP-expressing areas were identified using the threshold feature of ImageJ. After subtracting the background fluorescence (subtraction of gray values of non-expressing pixels from every pixel) in the respective red and green channels, GFP intensity was calculated by multiplying the mean grayscale value per pixel by the total number of GFP-expressing pixels in each channel, and then adding those values for both the red and green channels. GFP Intensity values were collected for all 100 time points to yield expression profiles. Variations in GFP expression profiles resulted from differences in factors such as promoter strength, presence of a silencing suppressor, or nature of the promoter. In addition to quantification of GFP intensity, the image series were also used to generate time-lapse animations using ImageReady. Time-lapse animations revealed that the clear majority of cells displayed a relatively rapid increase in GFP expression, followed by a slow decline. Some cells occasionally displayed a sudden loss of fluorescence, which may be associated with rapid cell death. Apparent transport of GFP across the membrane and cell wall to adjacent cells was also observed. Time lapse animations provided additional information that could not otherwise be obtained using GFP Intensity profiles or single time point image collections

Access to and experience of later abortion: accounts from women in Scotland

Context: Except in the presence of significant medical indications, the legal limit for abortion in Great Britain is 24 weeks’ gestation. Nevertheless, abortion for nonmedical reasons is not usually provided in Scotland after 18–20 weeks, meaning women have to travel to England for the procedure. Methods: In-depth interviews were conducted with 23 women presenting for "later" abortions (i.e., at 16 or more weeks’ gestation) in Scotland. Participants were women who sought an abortion at a participating National Health Service clinic between January and July 2013. Interviews addressed reasons for and consequences of later presentation, as well as women's experiences of abortion. Thematic analysis attended to emerging issues and employed the conceptual tool of candidacy. Results: Delayed recognition of pregnancy, changed life circumstances and conflicting candidacies for motherhood and having an abortion were common reasons for women's presentation for later abortion. Women perceived that the resources required to travel to England for a later abortion were potential barriers to access, and felt that such travel was distressing and stigmatizing. Participants who continued their pregnancy did so after learning they were at a later gestational age than expected or after receiving assurances of support from partners, friends or family. Conclusions: Reasons for seeking later abortion are complex and varied among women in Scotland, and suggest that reducing barriers to access and improving local provision of such abortions are a necessity. The candidacy framework allows for a fuller understanding of the difficulties involved in obtaining abortions

Cooperative Transport of Brownian Particles

We consider the collective motion of finite-sized, overdamped Brownian particles (e.g., motor proteins) in a periodic potential. Simulations of our model have revealed a number of novel cooperative transport phenomena, including (i) the reversal of direction of the net current as the particle density is increased and (ii) a very strong and complex dependence of the average velocity on both the size and the average distance of the particles.Comment: 4 pages, 5 figure

Predicting and harnessing protein flexibility in the design of species-specific inhibitors of thymidylate synthase1,21Escherichia coli thymidylate synthase numbering is used unless otherwise noted.2PDB coordinates have been deposited with the RCSB with accession ID: 1JG0.

AbstractBackground: Protein plasticity in response to ligand binding abrogates the notion of a rigid receptor site. Thus, computational docking alone misses important prospective drug design leads. Bacterial-specific inhibitors of an essential enzyme, thymidylate synthase (TS), were developed using a combination of computer-based screening followed by in-parallel synthetic elaboration and enzyme assay [Tondi et al. (1999) Chem. Biol. 6, 319–331]. Specificity was achieved through protein plasticity and despite the very high sequence conservation of the enzyme between species.Results: The most potent of the inhibitors synthesized, N,O-didansyl-L-tyrosine (DDT), binds to Lactobacillus casei TS (LcTS) with 35-fold higher affinity and to Escherichia coli TS (EcTS) with 24-fold higher affinity than to human TS (hTS). To reveal the molecular basis for this specificity, we have determined the crystal structure of EcTS complexed with DDT and 2′-deoxyuridine-5′-monophosphate (dUMP). The 2.0 Å structure shows that DDT binds to EcTS in a conformation not predicted by molecular docking studies and substantially differently than other TS inhibitors. Binding of DDT is accompanied by large rearrangements of the protein both near and distal to the enzyme’s active site with movement of Cα carbons up to 6 Å relative to other ternary complexes. This protein plasticity results in novel interactions with DDT including the formation of hydrogen bonds and van der Waals interactions to residues conserved in bacterial TS but not hTS and which are hypothesized to account for DDT’s specificity. The conformation DDT adopts when bound to EcTS explains the activity of several other LcTS inhibitors synthesized in-parallel with DDT suggesting that DDT binds to the two enzymes in similar orientations.Conclusions: Dramatic protein rearrangements involving both main and side chain atoms play an important role in the recognition of DDT by EcTS and highlight the importance of incorporating protein plasticity in drug design. The crystal structure of the EcTS/dUMP/DDT complex is a model system to develop more selective TS inhibitors aimed at pathogenic bacterial species. The crystal structure also suggests a general formula for identifying regions of TS and other enzymes that may be treated as flexible to aid in computational methods of drug discovery