Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive and devastating neurodegenerative condition for which there are no effective treatments. Understanding the molecular pathology of AD during disease progression may identify new ways to reduce neuronal damage. Here, we present a longitudinal study tracking dynamic proteomic alterations in the brains of an inducible Drosophila melanogaster model of AD expressing the Arctic mutant Aβ42 gene. We identified 3093 proteins from flies that were induced to express Aβ42 and age-matched healthy controls using label-free quantitative ion-mobility data independent analysis mass spectrometry. Of these, 228 proteins were significantly altered by Aβ42 accumulation and were enriched for AD-associated processes. Network analyses further revealed that these proteins have distinct hub and bottleneck properties in the brain protein interaction network, suggesting that several may have significant effects on brain function. Our unbiased analysis provides useful insights into the key processes governing the progression of amyloid toxicity and forms a basis for further functional analyses in model organisms and translation to mammalian systems

Explaining trends in Scottish coronary heart disease mortality between 2000 and 2010 using IMPACTSEC model: retrospective analysis using routine data.

Objective To quantify the contributions of prevention and treatment to the trends in mortality due to coronary heart disease in Scotland. Design Retrospective analysis using IMPACTSEC, a previously validated policy model, to apportion the recent decline in coronary heart disease mortality to changes in major cardiovascular risk factors and to increases in more than 40 treatments in nine non-overlapping groups of patients. Setting Scotland. Participants All adults aged 25 years or over, stratified by sex, age group, and fifths of Scottish Index of Multiple Deprivation. Main outcome measure Deaths prevented or postponed. Results 5770 fewer deaths from coronary heart disease occurred in 2010 than would be expected if the 2000 mortality rates had persisted (8042 rather than 13813). This reflected a 43% fall in coronary heart disease mortality rates (from 262 to 148 deaths per 100000). Improved treatments accounted for approximately 43% (95% confidence interval 33% to 61%) of the fall in mortality, and this benefit was evenly distributed across deprivation fifths. Notable treatment contributions came from primary prevention for hypercholesterolaemia (13%), secondary prevention drugs (11%), and chronic angina treatments (7%). Risk factor improvements accounted for approximately 39% (28% to 49%) of the fall in mortality (44% in the most deprived fifth compared with only 36% in the most affluent fifth). Reductions in systolic blood pressure contributed more than one third (37%) of the decline in mortality, with no socioeconomic patterning. Smaller contributions came from falls in total cholesterol (9%), smoking (4%), and inactivity (2%). However, increases in obesity and diabetes offset some of these benefits, potentially increasing mortality by 4% and 8% respectively. Diabetes showed strong socioeconomic patterning (12% increase in the most deprived fifth compared with 5% for the most affluent fifth). Conclusions Increases in medical treatments accounted for almost half of the large recent decline in mortality due to coronary heart disease in Scotland. Furthermore, the Scottish National Health Service seems to have delivered these benefits equitably. However, the substantial contributions from population falls in blood pressure and other risk factors were diminished by adverse trends in obesity and diabetes. Additional population-wide interventions are urgently needed to reduce coronary heart disease mortality and inequalities in future decades

Anthropometry, dietary intake, physical activity and sitting time patterns in adolescents aged 15-17 years: an international comparison in eight Latin American countries

BACKGROUND: Although there is high prevalence of obesity and other cardiovascular risk factors among Latin American adolescents, there is limited evidence on dietary intake and physical activity (PA) patterns in this population. Therefore, we characterized anthropometry, dietary intake, PA and sitting time (ST) in adolescents aged 15-17 years from eight Latin American countries. METHODS: Six hundred seventy-one adolescents (41.4% girls) from the Latin American Study of Nutrition and Health (ELANS) were included. Nutritional status was classified by four BMI (kg/m2) categories. Waist circumference (WC) was categorized as above or below thresholds. Dietary intake was assessed through two non-consecutive 24-h dietary recalls. PA and ST were measured using the International Physical Activity Questionnaire (IPAQ). We calculated overall and country-specific estimates by sex and tested for differences between boys and girls. RESULTS: Differences in the prevalence of overweightness (15.1 and 21.6%) and obesity (8.5 and 6.5%) between boys and girls, respectively, were statistically insignificant (p = 0.059). Average energy intake was 2289.7 kcal/day (95% CI: 2231-2350) for boys and 1904.2 kcal/day (95% CI: 1840-1963) for girls (p  0.05 for all outcomes). There was no statistically significant difference in the prevalence of total energy (TE) saturated fat and added sugar (>10% of TE) between girls and boys (49.6% versus 44.8 and 81.7% versus 76.1%, respectively). Prevalence of physical inactivity was 19% in boys and 43.7% in girls (p  0.05). CONCLUSIONS: These findings highlight the high prevalence of poor dietary intake and physical inactivity in adolescents from Latin American countries. Therefore, effective and sustainable strategies and programmes are needed that promote healthier diets, regular PA and reduce ST among Latin American adolescents. TRIAL REGISTRATION: Clinical Trials NCT02226627. Retrospectively registered on August 27, 2014

The charcoal trap: Miombo forests and the energy needs of people

<p>Abstract</p> <p>Background</p> <p>This study evaluates the carbon dioxide and other greenhouse gas fluxes to the atmosphere resulting from charcoal production in Zambia. It combines new biomass and flux data from a study, that was conducted in a <it>miombo </it>woodland within the Kataba Forest Reserve in the Western Province of Zambia, with data from other studies.</p> <p>Results</p> <p>The measurements at Kataba compared protected area (3 plots) with a highly disturbed plot outside the forest reserve and showed considerably reduced biomass after logging for charcoal production. The average aboveground biomass content of the reserve (Plots 2-4) was around 150 t ha^-1, while the disturbed plot only contained 24 t ha^-1. Soil carbon was not reduced significantly in the disturbed plot. Two years of eddy covariance measurements resulted in net ecosystem exchange values of -17 ± 31 g C m^-2y^-1, in the first and 90 ± 16 g C m^-2in the second year. Thus, on the basis of these two years of measurement, there is no evidence that the <it>miombo </it>woodland at Kataba represents a present-day carbon sink. At the country level, it is likely that deforestation for charcoal production currently leads to a per capita emission rate of 2 - 3 t CO₂y^-1. This is due to poor forest regeneration, although the resilience of <it>miombo </it>woodlands is high. Better post-harvest management could change this situation.</p> <p>Conclusions</p> <p>We argue that protection of <it>miombo </it>woodlands has to account for the energy demands of the population. The production at national scale that we estimated converts into 10,000 - 15,000 GWh y^-1of energy in the charcoal. The term "Charcoal Trap" we introduce, describes the fact that this energy supply has to be substituted when woodlands are protected. One possible solution, a shift in energy supply from charcoal to electricity, would reduce the pressure of forests but requires high investments into grid and power generation. Since Zambia currently cannot generate this money by itself, the country will remain locked in the charcoal trap such as many other of its African neighbours. The question arises whether and how money and technology transfer to increase regenerative electrical power generation should become part of a post-Kyoto process. Furthermore, better inventory data are urgently required to improve knowledge about the current state of the woodland usage and recovery. Net greenhouse gas emissions could be reduced substantially by improving the post-harvest management, charcoal production technology and/or providing alternative energy supply.</p

Complexity in water and carbon dioxide fluxes following rain pulses in an African savanna

The idea that many processes in arid and semi-arid ecosystems are dormant until activated by a pulse of rainfall, and then decay from a maximum rate as the soil dries, is widely used as a conceptual and mathematical model, but has rarely been evaluated with data. This paper examines soil water, evapotranspiration (ET), and net ecosystem CO2 exchange measured for 5 years at an eddy covariance tower sited in an Acacia–Combretum savanna near Skukuza in the Kruger National Park, South Africa. The analysis characterizes ecosystem flux responses to discrete rain events and evaluates the skill of increasingly complex “pulse models”. Rainfall pulses exert strong control over ecosystem-scale water and CO2 fluxes at this site, but the simplest pulse models do a poor job of characterizing the dynamics of the response. Successful models need to include the time lag between the wetting event and the process peak, which differ for evaporation, photosynthesis and respiration. Adding further complexity, the time lag depends on the prior duration and degree of water stress. ET response is well characterized by a linear function of potential ET and a logistic function of profile-total soil water content, with remaining seasonal variation correlating with vegetation phenological dynamics (leaf area). A 1- to 3-day lag to maximal ET following wetting is a source of hysteresis in the ET response to soil water. Respiration responds to wetting within days, while photosynthesis takes a week or longer to reach its peak if the rainfall was preceded by a long dry spell. Both processes exhibit nonlinear functional responses that vary seasonally. We conclude that a more mechanistic approach than simple pulse modeling is needed to represent daily ecosystem C processes in semiarid savannas

Socio-demographic patterning of objectively measured physical activity and sedentary behaviours in eight Latin American countries: findings from the ELANS study

Physical activity (PA) and sedentary behaviours (SB) are two independent risk factors for non-communicable diseases. However, there is a lack of objectively measured information on PA and SB in low- and middle-income countries. The aim of this study was to use objective data to characterise socio-demographic patterns of PA and SB in eight Latin American countries. 2,732 participants (aged 15-65 years) from the Latin American Study of Nutrition and Health (ELANS) were included. PA and SB data were collected using accelerometers. Overall and country-specific average levels of time spent in PA and SB were compared by sex, age, socioeconomic and education level. Overall, the mean time spent in SB was 571.6 min/day, ranging from 553.8 min/day in Chile to 596.7 min/day in Peru. Average levels of light, moderate-to-vigorous physical activity (MVPA) and total PA were 311.1 min/day (95% CI: 307.7; 314.5), 34.9 min/day (95% CI: 34.0; 35.9) and 7531.2 MET-min/week (95% CI: 7450.4; 7611.9), respectively. MVPA and total PA were higher in men than women. The prevalence of physical inactivity was 40.6%, ranging from 26.9% (Chile) to 47% (Costa Rica and Venezuela). Women were more physically inactive than men (47.7% versus 33.0%). SB levels were highest among those with higher education; PA graded positively with socioeconomic level. Our findings can inform the planning of health policies and programmes designed to reduce levels of physical inactivity, as well as inform the local and cultural adaptation of these policies and programmes for implementation in Latin America

Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults

BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPAL as criterion measure. Spearman correlations and Bland-Altman plots (or non-parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test-retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68-0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPAL were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPAL, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, -6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB

Efficacy of interventions to increase the uptake of chlamydia screening in primary care: a systematic review

<p>Abstract</p> <p>Background</p> <p>As most genital chlamydia infections are asymptomatic, screening is the main way to detect and cases for treatment. We undertook a systematic review of studies assessing the efficacy of interventions for increasing the uptake of chlamydia screening in primary care.</p> <p>Methods</p> <p>We reviewed studies which compared chlamydia screening in the presence and the absence of an intervention. The primary endpoints were screening rate or total tests.</p> <p>Results</p> <p>We identified 16 intervention strategies; 11 were randomised controlled trials and five observational studies, 10 targeted females only, five both males and females, and one males only. Of the 15 interventions among females, six were associated with significant increases in screening rates at the 0.05 level including a multifaceted quality improvement program that involved provision of a urine jar to patients at registration (44% in intervention clinics vs. 16% in the control clinic); linking screening to routine Pap smears (6.9% vs. 4.5%), computer alerts for doctors (12.2% vs. 10.6%); education workshops for clinic staff; internet-based continuing medical education (15.5% vs. 12.4%); and free sexual health consultations (16.8% vs. 13.2%). Of the six interventions targeting males, two found significant increases including the multifaceted quality improvement program in which urine jars were provided to patients at registration (45% vs. 15%); and the offering by doctors of a test to all presenting young male clients, prior to consultation (29 vs. 4%).</p> <p>Conclusions</p> <p>Interventions that promoted the universal offer of a chlamydia test in young people had the greatest impact on increasing screening in primary care.</p

CATH: expanding the horizons of structure-based functional annotations for genome sequences

This article provides an update of the latest data and developments within the CATH protein structure classification database (http://www.cathdb.info). The resource provides two levels of release: CATH-B, a daily snapshot of the latest structural domain boundaries and superfamily assignments, and CATH+, which adds layers of derived data, such as predicted sequence domains, functional annotations and functional clustering (known as Functional Families or FunFams). The most recent CATH+ release (version 4.2) provides a huge update in the coverage of structural data. This release increases the number of fully- classified domains by over 40% (from 308 999 to 434 857 structural domains), corresponding to an almost two- fold increase in sequence data (from 53 million to over 95 million predicted domains) organised into 6119 superfamilies. The coverage of high-resolution, protein PDB chains that contain at least one assigned CATH domain is now 90.2% (increased from 82.3% in the previous release). A number of highly requested features have also been implemented in our web pages: allowing the user to view an alignment between their query sequence and a representative FunFam structure and providing tools that make it easier to view the full structural context (multi-domain architecture) of domains and chains

Effects of a short individually tailored counselling session for HIV prevention in gay and bisexual men receiving Hepatitis B vaccination

Background. There is currently a trend towards unsafe unprotected anal intercourse (UAI) among men who have sex with men. We evaluated a short individual counselling session on reducing UAI among gay and bisexual men. Methods. A quasi-experimental design was used to evaluate the counselling session. This session was conducted during consulting hours at four municipal health clinics during a Hepatitis B vaccination campaign. These clinics offered free vaccination to high-risk groups, such as gay and bisexual men. All gay and bisexual men attending health clinics in four cities in the Netherlands were asked to participate. Each participant in the intervention group received a fifteen-minute individual counselling based on the Theory of Planned Behaviour and Motivational Interviewing. Changes in UAI were measured over a 5-months period, using self-administered questionnaires. UAI was measured separately for receptive and insertive intercourse in steady and casual partners. These measures were combined in an index-score (range 0-8). Results. While UAI in the counselling group remained stable, it increased in the controls by 66% from 0.41 to 0.68. The results show that the intervention had a protective effect on sexual behaviour with steady partners. Intervention effects were strongest within steady relationships, especially for men whose steady-relationship status changed during the study. The intervention was well accepted among the target group. Conclusion. The fifteen-minute individually tailored counselling session was not only well accepted but also had a protective effect on risk behaviour after a follow-up of six months