331 research outputs found
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
No full textTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause
Interactions of dietary whole-grain intake with fasting glucose-and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies
No full textObjective: Whole grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Research Design & Methods: Via meta-analysis of data from 14 cohorts comprising approximately 48,000 participants of European descent, we studied interactions of whole grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a p-value <0.0028 (0.05/18 tests) as statistically significant. Results: Greater whole grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (? [95% CI] per 1-serving greater whole grain intake: ?0.009 mmol/L glucose [?0.013, ?0.005], p <0.0001 and ?0.011 pmol/L (ln) insulin [?0.015, ?0.007], p =0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole grain intake was rs780094 (GCKR) for fasting insulin (p = 0.006), where greater whole grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Conclusions: Our results support the favorable association of whole grain intake with fasting glucose and insulin and suggest potential interaction between variation in GCKR and whole grain intake in influencing fasting insulin concentrations. <br/
Measurement and modeling of short- and long-term commuter exposure to traffic-related air pollution
No full textBackground. Many epidemiological studies have reported associations between traffic-related air pollu¬tion exposure and acute and chronic health problems. Exposure assignment in those stud¬ies has typically relied on home outdoor locations and ignored exposure during commuting and at non-residential locations. However, because of high concentrations of harmful air pollutants in proximity to traffic, time spent in transport may contribute considerably to a person’s total daily exposure to traffic-related air pollution. An understanding of how activity patterns affect exposure to traffic-related air pollution in space and time is important for im¬proved exposure assessments.
Concentration levels and individuals’ exposures to harmful traffic-related air pollutants in the various transport microenvironments are not well understood. Recently, exposure to ultrafine particles (UFP, particles smaller than 100 nm) has attracted particular interest. UFP are considered harmful to human health in view of their small size and the probability to penetrate deeply into the respiratory tract. Little is known about the variability in UFP concentrations and most notably the average particle size in various transport environ¬ments. This is largely due to the lack of a robust portable device to measure UFP charac¬teristics.
Objectives. The aim of this thesis was to characterize exposure to both UFP concentration and average particle size distribution diameters in commonly used transport environments in Basel. In addition, a simulation of commuter exposure to traffic-related air pollution of a general pop-ulation was carried out to estimate the contribution of commute (i.e., the time spent in traffic traveling between home and work or school) to total exposure and inhalation dose as well as its relevance in epidemiological studies on long-term health effects of traffic-related air pollution.
Methods. Three sub-studies were performed to characterize personal exposure to UFP concentration and average particle size distribution diameters in frequently traveled commuter microenvi-ronments. The personal monitoring campaign was carried out in the city of Basel and sur-rounding area between December 2010 and September 2011 using a newly developed portable device, the miniature Diffusion Size Classifier (miniDiSC), which measures particles in the size range of 10 to 300 nm. First, the spatial variation of sidewalk UFP exposures within urban areas and transport-specific microenvironments was explored. Measurements were conducted along four predefined walks once per month. Second, exposure to UFP concentration and average particle size were quantified for five modes of transportation (walking, bicycle, bus, tram, car) during different times of the day and week, along the same route. Finally, the contribution of bicycle commuting along two different routes (along main roads, away from main roads) to total daily exposures was assessed by 24-hour personal measurements. Measurements were equally distributed over weekdays (Monday to Friday) across three seasons – winter, spring and summer.
The simulation of commuter exposure to traffic-related air pollution was conducted based on spatially and temporally resolved data on commuter trips of residents working (or attending a school) within the Basel area (Cantons Basel-City and Basel-Country). The information on commuter routes, transportation modes and home, work and school locations were ex¬tracted from the year 2010 Swiss Mobility and Transport Microcensus survey. An approach to simulate travel routes based on the transportation mode and origin/destination location of the legs (pieces of the trips with the same transportation mode) was developed and vali¬dated. Individuals’ exposures to NO2 during commuting and at home, work and school loca¬tions were computed by overlapping the locations and travel routes with annual mean maps of NO2 in a geographic information system (GIS). Three air pollution models (a land use regression model (LUR), a high and a low resolution dispersion model) were evaluated for estimating commuter exposures to NO2 as a marker of long-term exposure to traffic-related air pollution. Finally, the bias in health effect estimates resulting from using home outdoor exposures only and ignoring other non-residential exposures including commuter exposure was quantified.
This thesis is part of the Europe-wide project, Transportation Air Pollution and Physical ActivitieS (TAPAS), which is an integrated health risk assessment program on climate change and urban policies.
Results. In general, smaller average particle sizes and higher UFP concentration levels were meas-ured at places and for transportation modes in close proximity to traffic. Average trip UFP concentrations were highest in car (31,800 particles cm-3) followed by bicycle (22,700 parti-cles cm-3), walking (19,500 particles cm-3) and public transportation (14,100-18,800 particles cm-3). Concentrations were highest for all transportation modes during weekday morning rush hours, compared to other time periods. UFP concentration was lowest in bus, regard¬less of time period. Average particle diameters followed an opposite trend than UFP con¬centration, showing larger average particle sizes for transportation modes and sampling times with lower UFP number concentrations and vice versa. Bicycle travel along main streets between home and work place (24 min on average) contributed 21% and 5% to total daily UFP exposure in winter and summer, respectively. Contribution of bicycle commutes to total daily UFP exposure could be reduced by half if main roads were avoided.
Within Basel-City, estimated average time-weighted NO2 population exposure during com-muting was similar among all air pollution models (around 39-41 µg m–3). The spatial varia-bility in NO2 concentrations, as typically encountered in urban street environments, was best reflected by the dispersion model with the highest resolution (grid size of 25 m). By com-parison, both the LUR model (applied to a 50x50 m grid) and the dispersion model with a lower resolution (100x100 m) underestimated the NO2 concentrations on the higher end, and overestimated the values on the lower end.
The population working (>= 50% work load) or attending a school within the region of Basel spent on average 49 minutes for daily commutes. Work or school occupied 22% of the subjects’ time on average. Median contribution of commuting to total weekly NO2 exposure was 2.7% (range 0.1-13.5%). With regard to inhalation dose, the commute contributed slightly more when assuming moderate (3.5%, range: 0.2-16.8%) or high (4.2%, range: 0.2-33.0%) breathing rates during active transportation. The median contribution of commute to the total NO2 exposure was highest for subjects using mainly public transportation (4.7%, range: 1.3-13.5%) who also spent the longest time in traffic (more than an hour). The com¬parison between the transportation modes based on the legs of the trips, however, revealed the highest NO2 exposures for motorized transportation.
The failure to differentiate between outdoor NO2 exposure at work/school and at home could result in a 12% (95%-CI: 11-14%) underestimation of related health effects. This bias was stronger for the subjects commuting between Basel-City and the rural to suburban sur-rounding areas of Basel-Country (33% underestimation) than for the subjects commuting within those areas. For the same population sub-group, potentially significant underestima¬tion of health effects (5%, 95%-CI: 4-5%) attributable to including outdoor exposures at home and at work/school but omitting exposure during the commute was found.
Conclusions and Outlook. This thesis provides important insights in the spatial and temporal variability of UFP within an urban area and provides an approach for modeling commuter exposures to traffic-related air pollution in epidemiological studies. Results confirmed the expectation that people are exposed to potentially high exposures during their daily travels and that ignoring time-activity patterns in epidemiological studies results in exposure misclassification and bias associated health effects.
The benefit of incorporating non-residential locations and daily commute patterns in expo¬sure assignments of future epidemiological studies should carefully be evaluated based on (1) spatial and temporal variability of the pollutants of interest, and (2) the spatial spread of home and work/school locations and subjects’ level of mobility. Improved exposure estima¬tion thus requires information on subjects’ travel duration, distance, transportation modes, trip timings, route choices and work load.
Future exposure assessments of large cohorts will need to more frequently combine mod¬eling approaches with actual personal exposure measurements of pollutants of interest to refine and validate exposure estimates spatially as well as temporally
Pre-cooling for endurance exercise performance in the heat: a systematic review
No full textAbstract Background Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research. Methods The MEDLINE, EMBASE, CINAHL, Web of Science and SPORTDiscus databases were searched in May 2012 for studies evaluating the effectiveness of pre-cooling to enhance endurance exercise performance in hot environmental conditions (≥ 28°C). Studies involving participants with increased susceptibility to heat strain, cooling during or between bouts of exercise, and protocols where aerobic endurance was not the principle performance outcome were excluded. Potential publications were assessed by two independent reviewers for inclusion and quality. Means and standard deviations of exercise performance variables were extracted or sought from original authors to enable effect size calculations. Results In all, 13 studies were identified. The majority of studies contained low participant numbers and/or absence of sample size calculations. Six studies used cold water immersion, four crushed ice ingestion and three cooling garments. The remaining study utilized mixed methods. Large heterogeneity in methodological design and exercise protocols was identified. Effect size calculations indicated moderate evidence that cold water immersion effectively improved endurance performance, and limited evidence that ice slurry ingestion improved performance. Cooling garments were ineffective. Most studies failed to document or report adverse events. Low participant numbers in each study limited the statistical power of certain reported trends and lack of blinding could potentially have introduced either participant or researcher bias in some studies. Conclusions Current evidence indicates cold water immersion may be the most effective method of pre-cooling to improve endurance performance in hot conditions, although practicality must be considered. Ice slurry ingestion appears to be the most promising practical alternative. Interestingly, cooling garments appear of limited efficacy, despite their frequent use. Mechanisms behind effective pre-cooling remain uncertain, and optimal protocols have yet to be established. Future research should focus on standardizing exercise performance protocols, recruiting larger participant numbers to enable direct comparisons of effectiveness and practicality for each method, and ensuring potential adverse events are evaluated.</p
Mortality and progression to AIDS after starting highly active antiretroviral therapy.
No full textOBJECTIVES: To examine survival and progression to AIDS among HIV-infected patients after starting highly active antiretroviral therapy (HAART). METHODS: The study population consisted of 3724 patients from the ATHENA observational cohort who initiated HAART. We considered progression to either an AIDS-defining disease or death, distinguishing HIV-related and non-related (including therapy-related) deaths. A time-dependent multivariate hazards model was fitted to the patient data and 5-year survival probabilities under various therapy scenarios estimated. RESULTS: A total of 459 patients developed AIDS and 346 died during 12 503 person-years of follow-up. HIV-related mortality decreased from 3.8 to 0.7 per 100 person-years between 1996 and 2000 whereas non-HIV-related mortality did not change (0.4 and 0.9, respectively, P = 0.25). For asymptomatic and symptomatic therapy naive patients younger than 50 years with CD4 counts above 10 x 10(6) and 150 x 10(6) cells/l, respectively, predicted 5-year survival probabilities were above 90% when HAART was used continuously. This limit was 450 x 10(6) cells/l when HAART was used during 20 weeks in each 24 week-period of follow-up, and 110 x 10(6) cells/l when patients delayed initiation of HAART for 1 year after becoming eligible for treatment. CONCLUSIONS: Survival probabilities were high among HIV-infected patients initiating HAART at an early stage of infection. The best therapy strategy is therefore to start HAART at this stage of infection. However, deferring HAART in patients with high CD4 cell counts may be clinically more appropriate given toxicity and adherence problems. The lack of any change in non-HIV-related mortality suggests that toxicity has not yet become a major risk factor for death
Air pollution and subclinical airway inflammation in the SALIA cohort study
No full textThe association between long-term exposure to air pollution and local inflammation in the lung has rarely been investigated in the general population of elderly subjects before. We investigated this association in a population-based cohort of elderly women from Germany.; In a follow-up examination of the SALIA cohort study in 2008/2009, 402 women aged 68 to 79 years from the Ruhr Area and Borken (Germany) were clinically examined. Inflammatory markers were determined in exhaled breath condensate (EBC) and in induced sputum (IS). We used traffic indicators and measured air pollutants at single monitoring stations in the study area to assess individual traffic exposure and long-term air pollution background exposure. Additionally long-term residential exposure to air pollution was estimated using land-use regression (LUR) models. We applied multiple logistic and linear regression analyses adjusted for age, indoor mould, smoking, passive smoking and socio-economic status and additionally conducted sensitivity analyses.; Inflammatory markers showed a high variability between the individuals and were higher with higher exposure to air pollution. NO derivatives, leukotriene (LT) B4 and tumour necrosis factor-α (TNF-α) showed the strongest associations. An increase of 9.42 μg/m3 (interquartile range) in LUR modelled NO2 was associated with measureable LTB4 level (level with values above the detection limit) in EBC (odds ratio: 1.38, 95% CI: 1.02 -1.86) as well as with LTB4 in IS (%-change: 19%, 95% CI: 7% - 32%). The results remained consistent after exclusion of subpopulations with risk factors for inflammation (smoking, respiratory diseases, mould infestation) and after extension of models with additional adjustment for season of examination, mass of IS and urban/rural living as sensitivity analyses.; In this analysis of the SALIA study we found that long-term exposure to air pollutants from traffic and industrial sources was associated with an increase of several inflammatory markers in EBC and in IS. We conclude that long-term exposure to air pollution might lead to changes in the inflammatory marker profile in the lower airways in an elderly female population
Gender difference in HIV-1 RNA viral loads.
No full textOBJECTIVES: To test and characterize the dependence of viral load on gender in different countries and racial groups as a function of CD4 T-cell count. METHODS: Plasma viral load data were analysed for > 30,000 HIV-infected patients attending clinics in the USA [HIV Insight (Cerner Corporation, Vienna, VA, USA) and Plum Data Mining LLC (East Meadow, NY, USA) databases] and the Netherlands (Athena database; HIV Monitoring Foundation, Amsterdam, Netherlands). Log-normal regression models were used to test for an effect of gender on viral load while adjusting for covariates and allowing the effect to depend on CD4 T-cell count. Sensitivity analyses were performed to test the robustness of conclusions to assumptions regarding viral loads below the lower limit of quantification (LLOQ). RESULTS: After adjusting for covariates, women had (nonsignificantly) lower viral loads than men (HIV Insight: -0.053 log(10) HIV-1 RNA copies/mL, P = 0.202; Athena: -0.005 log(10) copies/mL, P = 0.667; Plum: -0.072 log(10) copies/mL, P = 0.273). However, further investigation revealed that the gender effect depended on CD4 T-cell count. Women had consistently higher viral loads than men when CD4 T-cell counts were at most 50 cells/microL, and consistently lower viral loads than men when CD4 T-cell counts were greater than 350 cells/microL. These effects were remarkably consistent when estimated independently for the racial groups with sufficient data available in the HIV Insight and Plum databases. CONCLUSIONS: The consistent relationship between gender-related differences in viral load and CD4 T-cell count demonstrated here explains the diverse findings previously published
Cultivo de microalgas chlorella vulgaris com efluente doméstico como meio de cultura alternativo
No full textTCC(graduação) - Universidade Federal de Santa Catarina. Centro Tecnológico. Engenharia Sanitária e Ambiental.O lançamento de esgoto em corpos d’água mesmo tratado pode resultar na poluição destes com uma carga rica em nutrientes fosfatados e nitrogenados, que acarreta eutrofização, entre outros problemas. As microalgas, micro-organismos fotossintetizantes, têm potencial para remover compostos inorgânicos das águas residuais e para produzir uma biomassa útil para a produção de biocombustíveis, fertilizantes e de outros bioprodutos. Dentro deste contexto, o presente trabalho teve o objetivo de avaliar o cultivo de microalgas da espécie Chlorella vulgaris com efluente doméstico como meio alternativo. O efluente doméstico foi coletado na Estação de Tratamento de Esgoto Lagoa da Conceição da CASAN, no município de Florianópolis, Santa Catarina. O procedimento metodológico dividiu-se em três etapas: isolamento da Chlorella vulgaris, teste com três espécies de microalgas (Desmodesmus sp., Chlorella vulgaris e Chlorococcales) cultivadas no efluente doméstico tratado como meio de cultura alternativo, e o experimento principal, no qual foi comparando o cultivo em meio de cultura sintético WC com o meio de cultura alternativo (efluente). Cada etapa durou em torno de 14 dias, com monitoramento do pH, turbidez e da biomassa de microalgas. No experimento principal também foi avaliada a remoção de nutrientes nitrogenados e fosfatados. Verificou-se que Chlorella vulgaris alcançou, na etapa 2, uma biomassa de 1,701 g/L, produtividade de 0,118 g/L/d, velocidade de crescimento de 0,369 divisões por dia, densidade celular de 5.200 x 104 células/ml
Pneumococcal serotype-specific antibodies persist through early childhood after infant immunization: follow-up from a randomized controlled trial
No full textBACKGROUND: In a previous UK multi-center randomized study 278 children received three doses of 7-valent (PCV-7) or 13-valent (PCV-13) pneumococcal conjugate vaccine at 2, 4 and 12 months of age. At 13 months of age, most of these children had pneumococcal serotype-specific IgG concentrations ?0.35 µg/ml and opsonophagocytic assay (OPA) titers ?8.METHODS:Children who had participated in the original study were enrolled again at 3.5 years of age. Persistence of immunity following infant immunization with either PCV-7 or PCV-13 and the immune response to a PCV-13 booster at pre-school age were investigated.RESULTS: In total, 108 children were followed-up to the age of 3.5 years and received a PCV-13 booster at this age. At least 76% of children who received PCV-7 or PCV-13 in infancy retained serotype-specific IgG concentrations ?0.35 µg/ml against each of 5/7 shared serotypes. For serotypes 4 and 18C, persistence was lower at 22-42%. At least 71% of PCV-13 group participants had IgG concentrations ?0.35 µg/ml against each of 4/6 of the additional PCV-13 serotypes; for serotypes 1 and 3 this proportion was 45% and 52%. In the PCV-7 group these percentages were significantly lower for serotypes 1, 5 and 7F. A pre-school PCV-13 booster was highly immunogenic and resulted in low rates of local and systemic adverse effects.CONCLUSION: Despite some decline in antibody from 13 months of age, these data suggest that a majority of pre-school children maintain protective serotype-specific antibody concentrations following conjugate vaccination at 2, 4 and 12 months of age
Association between traffic-related air pollution, subclinical inflammation and impaired glucose metabolism : results from the SALIA study
No full textEnvironmental and lifestyle factors regulate the expression and release of immune mediators. It has been hypothesised that ambient air pollution may be such an external factor and that the association between air pollution and impaired glucose metabolism may be attributable to inflammatory processes. Therefore, we assessed the associations between air pollution, circulating immune mediators and impaired glucose metabolism.; We analysed concentrations of 14 pro- and anti-inflammatory immune mediators as well as fasting glucose and insulin levels in plasma of 363 women from the Study on the influence of Air pollution on Lung function, Inflammation and Aging (SALIA, Germany). Exposure data for a group of pollutants such as nitrogen oxides (NO2, NOx) and different fractions of particulate matter were available for the participants' residences. We calculated the association between the pollutants and impaired glucose metabolism by multiple regression models.; The study participants had a mean age of 74.1 (SD 2.6) years and 48% showed impaired glucose metabolism based on impaired fasting glucose or previously diagnosed type 2 diabetes. Only long-term exposure NO2 and NOx concentrations showed positive associations (NO2: OR 1.465, 95% CI 1.049-2.046, NOx: OR 1.409, 95% CI 1.010-1.967) per increased interquartile range of NO2 (14.65 µg/m(3)) or NOx (43.16 µg/m(3)), respectively, but statistical significance was lost after correction for multiple comparisons. Additional adjustment for circulating immune mediators or the use of anti-inflammatory medication had hardly any impact on the observed ORs.; Our results suggest that exposure to nitrogen oxides may contribute to impaired glucose metabolism, but the associations did not reach statistical significance so that further studies with larger sample sizes are required to substantiate our findings. Our data do not preclude a role of inflammatory mechanisms in adipose or other tissues which may not be reflected by immune mediators in plasma
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