A pilot investigation to optimise methods for a future satiety preload study

Preload studies are used to investigate the satiating effects of foods and food ingredients. However, the design of preload studies is complex, with many methodological considerations influencing appetite responses. The aim of this pilot investigation was to determine acceptability, and optimise methods, for a future satiety preload study. Specifically, we investigated the effects of altering (i) energy intake at a standardised breakfast (gender-specific or non-gender specific), and (ii) the duration between mid-morning preload and ad libitum lunch meal, on morning appetite scores and energy intake at lunch. Participants attended a single study visit. Female participants consumed a 214-kcal breakfast (n = 10) or 266-kcal breakfast (n = 10), equivalent to 10% of recommended daily energy intakes for females and males, respectively. Male participants (n = 20) consumed a 266-kcal breakfast. All participants received a 250-ml orange juice preload 2 h after breakfast. The impact of different study timings was evaluated in male participants, with 10 males following one protocol (protocol 1) and 10 males following another (protocol 2). The duration between preload and ad libitum lunch meal was 2 h (protocol 1) or 2.5 h (protocol 2), with the ad libitum lunch meal provided at 12.00 or 13.00, respectively. All female participants followed protocol 2. Visual analogue scale (VAS) questionnaires were used to assess appetite responses and food/drink palatability. Correlation between male and female appetite scores was higher with the provision of a gender-specific breakfast, compared to non-gender-specific breakfast (Pearson correlation of 0.747 and 0.479, respectively). No differences in subjective appetite or ad libitum energy intake were found between protocols 1 and 2. VAS mean ratings of liking, enjoyment, and palatability were all > 66 out of 100 mm for breakfast, preload, and lunch meals. The findings of this pilot study confirm the acceptability of this methodology for future satiety preload studies. Appetite scores increased from preload to ad libitum lunch meal; however, no specific differences were found between protocols. The results highlight the importance of considering energy intake prior to preload provision, with a gender-specific breakfast improving the correlation between male and female appetite score responses to a morning preload

A Small Genomic Region Containing Several Loci Required for Gastrulation in Drosophila

Genetic screens in Drosophila designed to search for loci involved in gastrulation have identified four regions of the genome that are required zygotically for the formation of the ventral furrow. For three of these, the genes responsible for the mutant phenotypes have been found. We now describe a genetic characterization of the fourth region, which encompasses the cytogenetic interval 24C3-25B, and the mapping of genes involved in gastrulation in this region. We have determined the precise breakpoints of several existing deficiencies and have generated new deficiencies. Our results show that the region contains at least three different loci associated with gastrulation effects. One maternal effect gene involved in ventral furrow formation maps at 24F but could not be identified. For a second maternal effect gene which is required for germ band extension, we identify a candidate gene, CG31660, which encodes a G protein coupled receptor. Finally, one gene acts zygotically in ventral furrow formation and we identify it as Traf4

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Infrastructural support to promote farmer adoption of improved technologies.

The paper considers the factors responsible for technology adoption and suggests the infrastructures needed to hasten adoption. Case studies from Bangladesh are used to illustrate the beneficial effects of some of the infrastructural support systems on technology adoption

Parental health limitations, caregiving and loneliness among women with widowed parents: longitudinal eveidence from France

We investigate how daughters’ feelings of loneliness are impacted when widowed parents develop health limitations, and when daughters take on personal care tasks in response. Using longitudinal data from daughters of widowed parents drawn from the French Family and Intergenerational Relationships Study (ERFI, 1485 observations nested in 557 daughters), we assess (a) whether health limitations of widowed parents are associated with daughters’ feelings of loneliness regardless of whether or not daughters provide personal care and (b) whether there is an effect of care provision on loneliness that cannot be explained by parental health limitations. Fixed effect regression analyses show that widowed parents’ health limitations were associated with raised feelings of loneliness among their daughters. No significant additional effect of providing personal care to a widowed parent was found. Prior research on the impact of health limitations of older parents on the lives of their adult–children has focused mostly on issues related to informal caregiving. Our findings suggest that more attention to the psychosocial impact of parental health limitations—net of actual caregiving—on adult children’s lives is warranted

The RICORDO approach to semantic interoperability for biomedical data and models: strategy, standards and solutions.

BACKGROUND: The practice and research of medicine generates considerable quantities of data and model resources (DMRs). Although in principle biomedical resources are re-usable, in practice few can currently be shared. In particular, the clinical communities in physiology and pharmacology research, as well as medical education, (i.e. PPME communities) are facing considerable operational and technical obstacles in sharing data and models. FINDINGS: We outline the efforts of the PPME communities to achieve automated semantic interoperability for clinical resource documentation in collaboration with the RICORDO project. Current community practices in resource documentation and knowledge management are overviewed. Furthermore, requirements and improvements sought by the PPME communities to current documentation practices are discussed. The RICORDO plan and effort in creating a representational framework and associated open software toolkit for the automated management of PPME metadata resources is also described. CONCLUSIONS: RICORDO is providing the PPME community with tools to effect, share and reason over clinical resource annotations. This work is contributing to the semantic interoperability of DMRs through ontology-based annotation by (i) supporting more effective navigation and re-use of clinical DMRs, as well as (ii) sustaining interoperability operations based on the criterion of biological similarity. Operations facilitated by RICORDO will range from automated dataset matching to model merging and managing complex simulation workflows. In effect, RICORDO is contributing to community standards for resource sharing and interoperability.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

Colonization history of the western corn rootworm (Diabrotica virgifera virgifera) in North America: insights from random forest ABC using microsatellite data

First described from western Kansas, USA, the western corn rootworm, Diabrotica virgifera virgifera, is one of the worst pests of maize. The species is generally thought to be of Mexican origin and to have incidentally followed the expansion of maize cultivation into North America thousands of years ago. However, this hypothesis has never been investigated formally. In this study, the genetic variability of samples collected throughout North America was analysed at 13 microsatellite marker loci to explore precisely the population genetic structure and colonization history of D. v. virgifera. In particular, we used up-to-date approximate Bayesian computation methods based on random forest algorithms to test a Mexican versus a central-USA origin of the species, and to compare various possible timings of colonization. This analysis provided strong evidence that the origin of D. v. virgifera was southern (Mexico, or even further south). Surprisingly, we also found that the expansion of the species north of its origin was recent—probably not before 1100 years ago—thus indicating it was not directly associated with the early history of maize expansion out of Mexico, a far more ancient event

History of clinical transplantation

The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts