Weight change and quality of life in a community-based population

*Objectives:* This study investigates the longitudinal association between 5-year weight change and quality of life (QoL) in Dutch men and women.

*Design:* A prospective cohort study (1998, 2000, 2003) in a population based sample. Subjects: 2,414 men and women from the Maastricht region of the Netherlands.

*Measurements:* QoL outcomes were measured by the RAND-36 (eight subscales and two overall composite scores, physical and mental health (PCS and MCS)). Weight was measured on a scale. Weight change was calculated as change in weight between 1998 and 2003. In addition, 5-year weight change was also categorized in three groups: weight losers, weight maintainers, and weight gainers. All analyses were stratified for gender.

*Results:* A total of 598 men (50%) and 646 women (54%) maintained their weight, 177 men (15%) and 163 women (14%) lost more than 2.5 kg, and 410 men (35%) and 379 women (32%) gained more than 2.5 kg. Associations between 5-year weight change and QoL were found for MCS ([beta] = 0.13, 95% CI: 0.02|0.24) in women, and PCS ([beta] = -0.09, 95% CI: -0.17|-0.00; [beta] = -0.10, 95% CI: -0.19|-0.01) in men and women respectively. Moreover, associations between weight change and QoL were most pronounced for women of normal weight and obese men. Furthermore, in both genders, weight gainers showed a greater reduction on all physical components of QoL compared with weight maintainers. However, after 5-years weight gainers and weight losers did not significantly differ from weight maintainers in the mean change of MCS and PCS.

*Conclusion:* Weight gain was inversely associated with the physical domains of QoL in women and obese men. Conversely, in women, weight gain was positively associated with the mental domains of QoL. No differences between weight losers and weight gainers were found in mean change of QoL compared with weight maintainers

Cryo-FIB Machining: An Alternative to TEM Cryo-Sections Cut with Diamonds?

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7-August 11, 201

Five-year effect of community-based intervention Hartslag Limburg on quality of life: A longitudinal cohort study

<p>Abstract</p> <p>Background</p> <p>During the past decade, quality of life (QoL) has become an accepted measure of disease impact, therapeutic outcome, and evaluation of interventions. So far, very little is known about the effects of community-based interventions on people's QoL. Therefore, the effect of an integrative cardiovascular diseases community-based intervention programme 'Hartslag Limburg' on QoL after 5-years of intervention is studied.</p> <p>Methods</p> <p>A longitudinal cohort study comparing 5-year mean change in QoL between the intervention (n = 2356) and reference group (n = 758). QoL outcomes were the physical and mental health composite scores (PCS and MCS) measured by the RAND-36. Analyses were stratified for gender and socio-economic status (SES).</p> <p>Results</p> <p>After 5-years of intervention we found no difference in mean change in PCS and MCS between the intervention and reference group in both genders and low-SES. However, for the moderate/high SES intervention group, the scales social functioning (-3.6, 95% CI:-6.1 to -1.2), physical role limitations (-5.3, 95% CI:-9.6 to -1.0), general mental health (-3.0, 95% CI:-4.7 to -1.3), vitality (-3.2, 95% CI:-5.1 to -1.3), and MCS (-1.8, 95% CI:-2.9 to -0.6) significantly changed compared with the reference group. These differences were due to a slight decrease of QoL in the intervention group and an increase of QoL in the reference group.</p> <p>Conclusion</p> <p>Hartslag Limburg has no beneficial effect on people's physical and mental QoL after 5-years of intervention. In fact, subjects in the intervention group with a moderate/high SES, show a decrease on their mental QoL compared with the reference group.</p

Національна безпека України в епоху глобалізації

Розглядається сучасний проект Стратегії національної безпеки України “Україна в світі, що змінюється”, розроблений Національним інститутом стратегічних досліджень. Визначаються слабкі місця і невизначеності цієї стратегії. Проаналізовано реальний стан та перспективи впровадження цього проекту.In the article the modern is examined project of Strategy of national safety of Ukraine “Ukraine in the world that changes” worked out by the National institute of strategic. The weak locations and vaguenesses of this strategy are determined. An author analyses the real state and prospects of introduction of this project

Methods to assess the effect of meat processing on viability of Toxoplasma gondii: towards replacement of mouse bioassay by in vitro testing

Consumption of meat containing viable tissue cysts is considered one of the main sources of human infection with Toxoplasma gondii. In contrast to fresh meat, raw meat products usually undergo processing, including salting and mixing with other additives such as sodium acetate and sodium lactate, which affects the viability of T. gondii. However, the experiments described in the literature are not always performed in line with the current processing methods applied in industry. It was our goal to study the effect of salting and additives according to the recipes used by industrial producers. Mouse or cat bioassay is the ‘gold standard’ to demonstrate the presence of viable T. gondii. However, it is costly, time consuming and for ethical reasons not preferred for large-scale studies. Therefore, we first aimed to develop an alternative for mouse bioassay that can be used to determine the effect of processing on the viability of T. gondii tissue cysts. The assays studied were (i) a cell culture method to determine the parasite’s ability to multiply, and (ii) a propidium monoazide (PMA) dye-based assay to selectively detect DNA from intact parasites. Processing experiments were performed with minced meat incubated for 20 h with low concentrations of NaCl, sodium lactate and sodium acetate. NaCl appeared to be the most effective ingredient with only one or two out of eight mice infected after inoculation with pepsin-digest of portions processed with 1.0, 1.2 and 1.6% NaCl. Results of preliminary experiments with the PMA-based method were inconsistent and did not sufficiently discriminate between live and dead parasites. In contrast, the cell culture method showed promising results, but further optimization is needed before it can replace or reduce the number of mouse bioassays needed. In future, standardised in vitro methods are necessary to allow more extensive testing of product-specific processing methods, thereby providing a better indication of the risk of T. gondii infection for consumers

Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma

The efficacy of daratumumab depends partially on CD38 expression on multiple myeloma (MM) cells. We have previously shown that all-trans retinoic acid (ATRA) upregulates CD38 expression and reverts daratumumab-resistance ex vivo. We therefore evaluated the optimal dose, efficacy, and safety of daratumumab combined with ATRA in patients with daratumumab-refractory MM in a phase 1/2 study (NCT02751255). In part A of the study, 63 patients were treated with daratumumab monotherapy. Fifty patients with daratumumabrefractory MM were subsequently enrolled in part B and treated with daratumumab (reintensified schedule) combined with ATRA until disease progression. The recommended phase 2 dose of ATRA in combination with daratumumab was defined as 45 mg/m2. At this dose, the overall response rate (ORR) was 5%, indicating that the primary endpoint (ORR $15%) was not met. However, most patients (66%) achieved at least stable disease. After a median follow-up of 43 months, the median progression-free survival (PFS) for all patients was 2.8 months. Patients who previously achieved at least a partial response or minimal response/stable disease with prior daratumumab monotherapy had a significantly longer PFS compared with patients who immediately progressed during daratumumab as single agent (median PFS 3.4 and 2.8 vs 1.3 months). The median overall survival was 19.1 months. The addition of ATRA did not increase the incidence of adverse events. Flow cytometric analysis revealed that ATRA temporarily increased CD38 expression on immune cell subsets. In conclusion, the addition of ATRA and reintensification of daratumumab had limited activity in patients with daratumumab-refractory MM, which may be explained by the transient upregulation of CD38 expression. This trial was registered at www.clinicaltrials.gov as #NCT02751255

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

The cost-effectiveness of different visual acuity screening strategies in three European countries: a microsimulation study

Childhood vision screening programmes in Europe differ by age, frequency and location at which the child is screened, and by the professional who performs the test. The aim of this study is to compare the cost-effectiveness for three countries with different health care structures. We developed a microsimulation model of amblyopia. The natural history parameters were calibrated to a Dutch observational study. Sensitivity, specificity, attendance, lost to follow-up and costs in the three countries were based on the EUSCREEN Survey. Quality adjusted life-years (QALYs) were calculated using assumed utility loss for unilateral persistent amblyopia (1%) and bilateral visual impairment (8%). We calculated the cost-effectiveness of screening (with 3.5% annual discount) by visual acuity measurement at age 5 years or 4 and 5 years in the Netherlands by nurses in child healthcare centres, in England and Wales by orthoptists in schools and in Romania by urban kindergarten nurses. We compared screening at various ages and with various frequencies. Assuming an amblyopia prevalence of 36 per 1,000 children, the model predicted that 7.2 cases of persistent amblyopia were prevented in the Netherlands, 6.6 in England and Wales and 4.5 in Romania. The cost-effectiveness was €24,159, €19,981 and €23,589, per QALY gained respectively, compared with no screening. Costs/QALY was influenced most by assumed utility loss of unilateral persistent amblyopia. For all three countries, screening at age 5, or age 4 and 5 years were optimal. Despite differences in health care structure, vision screening by visual acuity measurement seemed cost-effective in all three countries

A Putative Plant Aminophospholipid Flippase, the Arabidopsis P4 ATPase ALA1, Localizes to the Plasma Membrane following Association with a β-Subunit

Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner leaflet and sphingolipids in the outer leaflet. This unequal distribution of lipids between leaflets is, amongst several proposed functions, hypothesized to be a prerequisite for endocytosis. P4 ATPases, belonging to the P-type ATPase superfamily of pumps, are involved in establishing lipid asymmetry across plasma membranes, but P4 ATPases have not been identified in plant plasma membranes. Here we report that the plant P4 ATPase ALA1, which previously has been connected with cold tolerance of Arabidopsis thaliana, is targeted to the plasma membrane and does so following association in the endoplasmic reticulum with an ALIS protein β-subunit

Inter-laboratory evaluation, development and validation of fungal preservation regimes used in different European biological resources centres (BRCs)

Successful preservation of fungi relies on the application of optimised preservation protocols that do not compromise the genomic integrity of the organism. Most major European BRCs use lyophilisation and cryopreservation as the methods of choice. Although based on generic principals, protocols can vary between institutions and do not always result in successful recovery. In order to evaluate the efficacy of the methods, a range of fungal strains were circulated around partner collections in the EMbaRC project and the organisms preserved using the standard methods used in each collection. The effectiveness of preservation was assessed using a series of techniques including DNA fingerprinting and sequencing, analysis of culture characteristics, viability assessments and the use of MALDI-TOF. The results showed that when viable cultures were obtained after preservation, they appeared to retain their genomic integrity, but there was evidence of delayed growth and attenuation in some cultures. Not all fungi were successfully preserved by all methods. It was found that a cryopreservation protocol used by the MUCL collection in Belgium, that limited manipulation of the fungus before preservation, was particularly effective in preserving some of the more delicate fungi and this method is being evaluated by the project partners. A further investigation was undertaken to assess the integrity of four specific strains of fungi deposited in different collections. They were compared using culture analysis, sequence analysis, DNA fingerprinting and MALDI-TOF. It was found that some limited variation was observed at the phenotypic level from the analysis of culture characteristics, but this could be expected, especially in organisms such as Aspergillus which can be prone to strain drift. More importantly, molecular integrity remained consistent with no significant differences observed between lines of the same strain. Therefore, despite the strains having been maintained by different methods over the intervening years from their initial deposit, the collections had maintained them in a stable manner. This is indicative of the benefits of applying proven regimes, resulting in high quality operations