Microencapsulated foods as a functional delivery vehicle for omega-3 fatty acids: a pilot study

It is well established that the ingestion of the omega-3 (N3) fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) positively benefit a variety of health indices. Despite these benefits the actual intake of fish derived N3 is relatively small in the United States. The primary aim of our study was to examine a technology capable of delivering omega-3 fatty acids in common foods via microencapsulation (MicroN3) in young, healthy, active participants who are at low risk for cardiovascular disease. Accordingly, we randomized 20 participants (25.4 ± 6.2 y; 73.4 ± 5.1 kg) to receive the double blind delivery of a placebo-matched breakfast meal (~2093 kJ) containing MicroN3 (450–550 mg EPA/DHA) during a 2-week pilot trial. Overall, we observed no differences in overall dietary macronutrient intake other than the N3 delivery during our treatment regimen. Post-test ANOVA analysis showed a significant elevation in mean (SE) plasma DHA (91.18 ± 9.3 vs. 125.58 ± 11.3 umol/L; P < 0.05) and a reduction in triacylglycerols (89.89 ± 12.8 vs. 80.78 ± 10.4 mg/dL; P < 0.05) accompanying the MicroN3 treatment that was significantly different from placebo (P < 0.05). In post study interviews, participants reported that the ingested food was well-tolerated, contained no fish taste, odor or gastrointestinal distress accompanying treatment. The use of MicroN3 foods provides a novel delivery system for the delivery of essential fatty acids. Our study demonstrates that MicroN3 foods promote the absorption of essential N3, demonstrate bioactivity within 2 weeks of ingestion and are well tolerated in young, active participants who are at low risk for cardiovascular disease

Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer

Background: Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.Methods: The pharmacokinetics of phenoxodiol was studied following a single intravenous (iv) bolus dose and during a continuous intravenous infusion. Three men with prostate cancer and 3 women with breast cancer received IV bolus phenoxodiol (5 mg/kg) and plasma was sampled for free and total phenoxodiol levels. On a separate occasion 5 of the same patients received a continuous intravenous infusion of phenoxodiol (2 mg/kg/h) and plasma was again sampled for free and total phenoxodiol levels. Phenoxodiol was measured using gradient HPLC with ultraviolet detection.Results: Following bolus injection, free and total phenoxodiol appeared to follow first order pharmacokinetics. The elimination half-lives for free and total phenoxodiol were 0.67 ± 0.53 h and 3.19 ± 1.93 h, respectively, while the total plasma clearance rates were 2.48 ± 2.33 L/h and 0.15 ± 0.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ± 0.69 L/kg and 0.64 ± 0.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ± 0.14 μg/ml after 0.87 ± 0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ± 0.04 h while the plasma clearance during continuous infusion was 1.29 ± 0.23 L/h.Conclusions: Phenoxodiol has a short plasma half-life, particularly in the free form, leading to a rapid attainment of steady state levels during continuous intravenous infusion.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334000

Common genetic variants on chromosome 9p21 are associated with myocardial infarction and type 2 diabetes in an Italian population

<p>Abstract</p> <p>Background</p> <p>A genomic region on chromosome 9p21 has been identified as closely associated with increased susceptibility to coronary artery disease (CAD) and to type 2 diabetes (T2D) although the evidence suggests that the genetic variants within chromosome 9p21 that contribute to CAD are different from those that contribute to T2D.</p> <p>We carried out an association case-control study in an Italian population to test the association between two single nucleotide polymorphisms (SNPs) on the 9p21 locus, rs2891168 and rs10811661, previously reported by the PROCARDIS study, and respectively myocardial infarction (MI) and T2D. Our aim was to confirm the previous findings on a larger sample and to verify the independence of their susceptibility effects: rs2891168 associated with MI but not with T2D and rs10811661 associated with T2D but not with MI.</p> <p>Methods</p> <p>Genomic DNA samples of 2407 Italians with T2D (602 patients), who had had a recent MI (600), or had both diseases (600) and healthy controls (605) were genotyped for the two SNPs. The genotypes were determined by allelic discrimination using a fluorescent-based TaqMan assay.</p> <p>Results</p> <p>SNP rs2891168 was associated with MI, but not with T2D and the G-allele odds ratio (OR) was 1.20 (95% CI 1.02-1.41); SNP rs10811661 was associated with T2D, but not with MI, and the T-allele OR was 1.27 (95% CI 1.04-1.55). ORs estimates from the present study and the PROCARDIS study were pooled and confirmed the previous findings, with greater precision.</p> <p>Conclusions</p> <p>Our replication study showed that rs2891168 and rs10811661 are independently associated respectively with MI and T2D in an Italian population. Pooling our results with those reported by the PROCARDIS group, we also obtained a significant result of association with diabetes for rs10811661 in the European population.</p

Factors influencing elderly women's mammography screening decisions: implications for counseling

<p>Abstract</p> <p>Background</p> <p>Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer, many older women with limited life expectancies are screened. We aimed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65–79.</p> <p>Methods</p> <p>Telephone surveys of 107 women aged 80+ and 93 women aged 65–79 randomly selected from one academic primary care practice who were able to communicate in English (60% response rate). The survey addressed the following factors in regards to older women's mammography screening decisions: perceived importance of a history of breast disease, family history of breast cancer, doctor's recommendations, habit, reassurance, previous experience, mailed reminder cards, family/friend's recommendations or experience with breast cancer, age, health, and media. The survey also assessed older women's preferred role in decision making around mammography screening.</p> <p>Results</p> <p>Of the 200 women, 65.5% were non-Hispanic white and 82.8% were in good to excellent health. Most (81.3%) had undergone mammography in the past 2 years. Regardless of age, older women ranked doctor's recommendations as the most important factor influencing their decision to get screened. Habit and reassurance were the next two highly ranked factors influencing older women to get screened. Among women who did not get screened, women aged 80 and older ranked age and doctor's counseling as the most influential factors and women aged 65–79 ranked a previous negative experience with mammography as the most important factor. There were no significant differences in preferred role in decision-making around mammography screening by age, however, most women in both age groups preferred to make the final decision on their own (46.6% of women aged 80+ and 50.5% of women aged 65–79).</p> <p>Conclusion</p> <p>While a doctor's recommendation is the most important factor influencing elderly women's mammography screening decisions, habit and reassurance also strongly influence decision-making. Interventions aimed at improving clinician counseling about mammography, which include discussions around habit and reassurance, may result in better decision-making.</p

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Specific Appetite for Carotenoids in a Colorful Bird

Background: Since carotenoids have physiological functions necessary for maintaining health, individuals should be selected to actively seek and develop a specific appetite for these compounds. Methodology/Principal Findings: Great tits Parus major in a diet choice experiment, both in captivity and the field, preferred carotenoid-enriched diets to control diets. The food items did not differ in any other aspects measured besides carotenoid content. Conclusions/Significance: Specific appetite for carotenoids is here demonstrated for the first time, placing these compounds on a par with essential nutrients as sodium or calcium

Genome-Wide Profiling of MicroRNAs in Adipose Mesenchymal Stem Cell Differentiation and Mouse Models of Obesity

In recent years, there has been accumulating evidence that microRNAs are key regulator molecules of gene expression. The cellular processes that are regulated by microRNAs include e.g. cell proliferation, programmed cell death and cell differentiation. Adipocyte differentiation is a highly regulated cellular process for which several important regulating factors have been discovered, but still not all are known to fully understand the underlying mechanisms. In the present study, we analyzed the expression of 597 microRNAs during the differentiation of mouse mesenchymal stem cells into terminally differentiated adipocytes by real-time RT-PCR. In total, 66 miRNAs were differentially expressed in mesenchymal stem cell-derived adipocytes compared to the undifferentiated progenitor cells. To further study the regulation of these 66 miRNAs in white adipose tissue in vivo and their dependence on PPARγ activity, mouse models of genetically or diet induced obesity as well as a mouse line expressing a dominant negative PPARγ mutant were employed

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

A programme of studies including assessment of diagnostic accuracy of school hearing screening tests and a cost-effectiveness model of school entry hearing screening programmes

Background Identification of permanent hearing impairment at the earliest possible age is crucial to maximise the development of speech and language. Universal newborn hearing screening identifies the majority of the 1 in 1000 children born with a hearing impairment, but later onset can occur at any time and there is no optimum time for further screening. A universal but non-standardised school entry screening (SES) programme is in place in many parts of the UK but its value is questioned. Objectives To evaluate the diagnostic accuracy of hearing screening tests and the cost-effectiveness of the SES programme in the UK. Design Systematic review, case–control diagnostic accuracy study, comparison of routinely collected data for services with and without a SES programme, parental questionnaires, observation of practical implementation and cost-effectiveness modelling. Setting Second- and third-tier audiology services; community. Participants Children aged 4–6 years and their parents. Main outcome measures Diagnostic accuracy of two hearing screening devices, referral rate and source, yield, age at referral and cost per quality-adjusted life-year. Results The review of diagnostic accuracy studies concluded that research to date demonstrates marked variability in the design, methodological quality and results. The pure-tone screen (PTS) (Amplivox, Eynsham, UK) and HearCheck (HC) screener (Siemens, Frimley, UK) devices had high sensitivity (PTS ≥ 89%, HC ≥ 83%) and specificity (PTS ≥ 78%, HC ≥ 83%) for identifying hearing impairment. The rate of referral for hearing problems was 36% lower with SES (Nottingham) relative to no SES (Cambridge) [rate ratio 0.64, 95% confidence interval (CI) 0.59 to 0.69; p < 0.001]. The yield of confirmed cases did not differ between areas with and without SES (rate ratio 0.82, 95% CI 0.63 to 1.06; p = 0.12). The mean age of referral did not differ between areas with and without SES for all referrals but children with confirmed hearing impairment were older at referral in the site with SES (mean age difference 0.47 years, 95% CI 0.24 to 0.70 years; p < 0.001). Parental responses revealed that the consequences to the family of the referral process are minor. A SES programme is unlikely to be cost-effective and, using base-case assumptions, is dominated by a no screening strategy. A SES programme could be cost-effective if there are fewer referrals associated with SES programmes or if referrals occur more quickly with SES programmes. Conclusions A SES programme using the PTS or HC screener is unlikely to be effective in increasing the identified number of cases with hearing impairment and lowering the average age at identification and is therefore unlikely to represent good value for money. This finding is, however, critically dependent on the results of the observational study comparing Nottingham and Cambridge, which has limitations. The following are suggested: systematic reviews of the accuracy of devices used to measure hearing at school entry; characterisation and measurement of the cost-effectiveness of different approaches to the ad-hoc referral system; examination of programme specificity as opposed to test specificity; further observational comparative studies of different programmes; and opportunistic trials of withdrawal of SES programmes