Determinants of rapid weight gain during infancy: baseline results from the NOURISH randomised controlled trial

Background: Rapid weight gain in infancy is an important predictor of obesity in later childhood. Our aim was to determine which modifiable variables are associated with rapid weight gain in early life.Methods: Subjects were healthy infants enrolled in NOURISH, a randomised, controlled trial evaluating an intervention to promote positive early feeding practices. This analysis used the birth and baseline data for NOURISH. Birthweight was collected from hospital records and infants were also weighed at baseline assessment when they were aged 4-7 months and before randomisation. Infant feeding practices and demographic variables were collected from the mother using a self administered questionnaire. Rapid weight gain was defined as an increase in weight-for-age Z-score (using WHO standards) above 0.67 SD from birth to baseline assessment, which is interpreted clinically as crossing centile lines on a growth chart. Variables associated with rapid weight gain were evaluated using a multivariable logistic regression model.Results: Complete data were available for 612 infants (88% of the total sample recruited) with a mean (SD) age of 4.3 (1.0) months at baseline assessment. After adjusting for mother's age, smoking in pregnancy, BMI, and education and infant birthweight, age, gender and introduction of solid foods, the only two modifiable factors associated with rapid weight gain to attain statistical significance were formula feeding [OR = 1.72 (95%CI 1.01-2.94), P = 0.047] and feeding on schedule [OR = 2.29 (95%CI 1.14-4.61), P = 0.020]. Male gender and lower birthweight were non-modifiable factors associated with rapid weight gain.Conclusions: This analysis supports the contention that there is an association between formula feeding, feeding to schedule and weight gain in the first months of life. Mechanisms may include the actual content of formula milk (e.g. higher protein intake) or differences in feeding styles, such as feeding to schedule, which increase the risk of overfeeding.Trial Registration: Australian Clinical Trials Registry ACTRN12608000056392

Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically, transmission of pathogens and antibody development against FBS are possible. In this study, we investigated whether FBS can be substituted by human platelet lysate (PL) in ASC culture, without affecting functional capacities particularly important for cardiac repair application of ASC. We found that PL-cultured ASC had a significant 3-fold increased proliferation rate and a significantly higher attachment to tissue culture plastic as well as to endothelial cells compared with FBS-cultured ASC. PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both showed a comparable surface marker profile, with the exception of significantly higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed a significantly higher migration rate compared with FBS-cultured ASC in a transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to differentiate towards cardiomyocytes. In conclusion, this study showed that culturing ASC is more favorable in PL-supplemented medium compared with FBS-supplemented medium

Gene Disruption of Plasmodium falciparum p52 Results in Attenuation of Malaria Liver Stage Development in Cultured Primary Human Hepatocytes

Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS) can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS) depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use

Functional outcome in older adults with joint pain and comorbidity: design of a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Joint pain is a highly prevalent condition in the older population. Only a minority of the older adults consult the general practitioner for joint pain, and during consultation joint pain is often poorly recognized and treated, especially when other co-existing chronic conditions are involved. Therefore, older adults with joint pain and comorbidity may have a higher risk of poor functional outcome and decreased quality of life (QoL), and possibly need more attention in primary care. The main purpose of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to identify possible predictors of poor functional outcome. The study will also identify predictors of decreased QoL. The results will be used to develop prediction models for the early identification of subgroups at high risk of poor functional outcome and decreased QoL. This may contribute to better targeting of treatment and to more effective health care in this population.</p> <p>Methods/Design</p> <p>The study has been designed as a prospective cohort study, with measurements at baseline and after 6, 12 and 18 months. For the recruitment of 450 patients, 25 general practices will be approached. Patients are eligible for participation if they are 65 years or older, have at least two chronic conditions and report joint pain on most days. Data will be collected using various methods (i.e. questionnaires, physical tests, patient interviews and focus groups). We will measure different aspects of functioning (e.g. mobility, functional independence and participation) and QoL. Other measurements concern possible predictors of functioning and QoL (e.g. pain, co-existing chronic conditions, markers for frailty, physical performance, psychological factors, environmental factors and individual factors). Furthermore, health care utilization, health care needs and the meaning and impact of joint pain will be investigated from an older person's perspective.</p> <p>Discussion</p> <p>In this paper, we describe the protocol of a prospective cohort study in Dutch older adults with joint pain and comorbidity and discuss the potential strengths and limitations of the study.</p

Psychological Determinants of Consumer Acceptance of Personalised Nutrition in 9 European Countries

YesObjective: To develop a model of the psychological factors which predict people’s intention to adopt personalised nutrition. Potential determinants of adoption included perceived risk and benefit, perceived self-efficacy, internal locus of control and health commitment. Methods: A questionnaire, developed from exploratory study data and the existing theoretical literature, and including validated psychological scales was administered to N = 9381 participants from 9 European countries (Germany, Greece, Ireland, Poland, Portugal, Spain, the Netherlands, the UK, and Norway). Results: Structural equation modelling indicated that the greater participants’ perceived benefits to be associated with personalised nutrition, the more positive their attitudes were towards personalised nutrition, and the greater their intention to adopt it. Higher levels of nutrition self-efficacy were related to more positive attitudes towards, and a greater expressed intention to adopt, personalised nutrition. Other constructs positively impacting attitudes towards personalised nutrition included more positive perceptions of the efficacy of regulatory control to protect consumers (e.g. in relation to personal data protection), higher self-reported internal health locus of control, and health commitment. Although higher perceived risk had a negative relationship with attitude and an inverse relationship with perceived benefit, its effects on attitude and intention to adopt personalised nutrition was less influential than perceived benefit. The model was stable across the different European countries, suggesting that psychological factors determining adoption of personalised nutrition have generic applicability across different European countries. Conclusion: The results suggest that transparent provision of information about potential benefits, and protection of consumers’ personal data is important for adoption, delivery of public health benefits, and commercialisation of personalised nutrition.This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement n u 265494 (http://cordis.europa.eu/fp7/home_en.html). Food4Me is the acronym of the project ‘‘Personalised nutrition: an integrated analysis of opportunities and challenges’’ (http://www.food4me.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The APOA5 Trp19 allele is associated with metabolic syndrome via its association with plasma triglycerides

<p>Abstract</p> <p>Background</p> <p>The goal of the present study was to assess the effect of genetic variability at the APOA5/A4/C3/A1 cluster locus on the risk of metabolic syndrome.</p> <p>Methods</p> <p>The <it>APOA5 </it>Ser19Trp, <it>APOA5 </it>-12,238T>C, <it>APOA4 </it>Thr347Ser, <it>APOC3 </it>-482C>T and <it>APOC3 </it>3238C>G (<it>Sst</it>I) polymorphisms were analyzed in a representative population sample of 3138 men and women from France, including 932 individuals with metabolic syndrome and 2206 without metabolic syndrome, as defined by the NCEP criteria.</p> <p>Results</p> <p>Compared with homozygotes for the common allele, the odds ratio (OR) [95% CI] for metabolic syndrome was 1.30 [1.03–1.66] (<it>p </it>= 0.03) for <it>APOA5 </it>Trp19 carriers, 0.81 [0.69–0.95] (<it>p </it>= 0.01) for <it>APOA5 </it>-12,238C carriers and 0.84 [0.70–0.99] (<it>p </it>= 0.04) for <it>APOA4 </it>Ser347 carriers. Adjustment for plasma triglycerides, (but not for waist girth, HDL, blood pressure or glycemia – the other components of metabolic syndrome) abolished these associations and suggests that triglyceride levels explain the association with metabolic syndrome. There was no association between the <it>APOC3 </it>-482C>T or <it>APOC3 </it>3238C>G polymorphisms and metabolic syndrome. The decreased risk of metabolic syndrome observed in <it>APOA5 </it>-12,238C and <it>APOA4 </it>Ser347 carriers merely reflected the fact that the <it>APOA5 </it>Trp19 allele was in negative linkage disequilibrium with the common alleles of <it>APOA5 </it>-12,238T>C and <it>APOA4 </it>Thr347Ser polymorphisms.</p> <p>Conclusion</p> <p>The <it>APOA5 </it>Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.</p

Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women

Temperature Shift and Host Cell Contact Up-Regulate Sporozoite Expression of Plasmodium falciparum Genes Involved in Hepatocyte Infection

Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface proteins involved in hepatocyte invasion, while the other two were predominantly expressed during hepatic parasite development. The genome-wide up-regulation of expression observed supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes validated our approach as one means to determine the repertoire of proteins implicated during the early events of the Plasmodium infection, and in this case that of P. falciparum, the species responsible for the severest forms of malaria

Exposure-in-vivo containing interventions to improve work functioning of workers with anxiety disorder: a systematic review

<p>Abstract</p> <p>Background</p> <p>Anxiety disorders are associated with functional disability, sickness absence, and decreased productivity. Effective treatments of anxiety disorders can result in remission of symptoms. However the effects on work related outcomes are largely unknown. Exposure in vivo is potentially well fit to improve work-related outcomes. This study systematically reviews the effectiveness of exposure-in-vivo containing interventions in reducing work-related adverse outcomes in workers with anxiety disorders.</p> <p>Methods</p> <p>A systematic study search was conducted in Medline, Cinahl, Embase and Psycinfo. Two reviewers independently extracted data and from each study assessed the quality of evidence by using the GRADE approach. We performed a meta-analysis if data showed sufficient clinical homogeneity.</p> <p>Results</p> <p>Seven studies containing 11 exposure-in-vivo interventions were included. Four studies were focused on Obsessive Compulsive Disorder (OCD), two on Post Traumatic Stress Disorder (PTSD), and one on a mixed group of OCD and severe phobias. The studies were grouped according to type of anxiety disorder and subsequently according to type of comparisons. For OCD, exposure-in-vivo containing interventions can yield better work-related outcomes compared to medication (SSRIs) and relaxation but not better compared to response prevention. The results on anxiety outcomes were similar. The net contribution of exposure in vivo in two OCD intervention programs is also presented as a meta-analysis and shows significant positive results on work role limitations. The calculated pooled effect size with 95% confidence interval was 0.72 (0.28, 1.15). For PTSD, exposure-in-vivo containing interventions can yield better work-related and anxiety-related outcomes compared to a waiting-list but not better compared to imaginal exposure.</p> <p>Conclusions</p> <p>Exposure in vivo as part of an anxiety treatment can reduce work-related adverse outcomes in workers with OCD and PTSD better than various other anxiety treatments or a waiting-list. We recommend that it should be studied how the results of these studies can be transferred to the practice of occupational health professionals and how clinicians can make better use of them to improve work-related outcomes. In future research, priority should be given to high-quality randomised controlled trials (RCTs) in which exposure-in-vivo containing interventions are applied to a variety of anxiety disorders and compared with other clinical anxiety treatments such as SSRIs. Work-related outcomes, in particular work functioning and sickness absence, need to be assessed with reliable and valid measures.</p