| 1. |
- Franks, Paul, et al.
(author)
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Epigenetics and obesity: the devil is in the details
- 2010
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 8
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Journal article (other academic/artistic)abstract
- Obesity is a complex disease with multiple well-defined risk factors. Nevertheless, susceptibility to obesity and its sequelae within obesogenic environments varies greatly from one person to the next, suggesting a role for gene x environment interactions in the etiology of the disorder. Epigenetic regulation of the human genome provides a putative mechanism by which specific environmental exposures convey risk for obesity and other human diseases and is one possible mechanism that underlies the gene x environment/treatment interactions observed in epidemiological studies and clinical trials. A study published in BMC Medicine this month by Wang et al. reports on an examination of DNA methylation in peripheral blood leukocytes of lean and obese adolescents, comparing methylation patterns between the two groups. The authors identified two genes that were differentially methylated, both of which have roles in immune function. Here we overview the findings from this study in the context of those emerging from other recent genetic and epigenetic studies, discuss the strengths and weaknesses of the study and speculate on the future of epigenetics in chronic disease research. See research article: http://www.biomedcentral.com/1741-7015/8/87/abstract
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| 2. |
- Cotoi, Ovidiu, et al.
(author)
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Plasma procalcitonin is associated with all-cause and cancer mortality in apparently healthy men: a prospective population-based study.
- 2013
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 11:1
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Journal article (peer-reviewed)abstract
- The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovascular disease or cancer.
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| 3. |
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| 4. |
- Hall, Elin, et al.
(author)
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Effects of palmitate on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets.
- 2014
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 12:1
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Journal article (peer-reviewed)abstract
- Circulating free fatty acids are often elevated in patients with type 2 diabetes (T2D) and obese individuals. Chronic exposure to high levels of saturated fatty acids has detrimental effects on islet function and insulin secretion. Altered gene expression and epigenetics may contribute to T2D and obesity. However, there is limited information on whether fatty acids alter the genome-wide transcriptome profile in conjunction with DNA methylation patterns in human pancreatic islets. To dissect the molecular mechanisms linking lipotoxicity to impaired insulin secretion, we investigated the effects of a 48 h palmitate treatment in vitro on genome-wide mRNA expression and DNA methylation patterns in human pancreatic islets.
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| 5. |
- O'Neil, Adrienne, et al.
(author)
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The impact of statins on psychological wellbeing: a systematic review and meta-analysis
- 2012
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 10
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Research review (peer-reviewed)abstract
- Background: Cholesterol-lowering medications such as statins have anti-inflammatory and antioxidant properties, which may be beneficial for treating depression and improving mood. However, evidence regarding their effects remains inconsistent, with some studies reporting links to mood disturbances. We aimed to conduct a meta-analysis to determine the impact of statins on psychological wellbeing of individuals with or without hypercholesterolemia. Methods: Articles were identified using medical, health, psychiatric and social science databases, evaluated for quality, and data were synthesized and analyzed in RevMan-5 software using a random effects model. Results: The 7 randomized controlled trials included in the analysis represented 2,105 participants. A test for overall effect demonstrated no statistically significant differences in psychological wellbeing between participants receiving statins or a placebo (standardized mean difference (SMD) = -0.08, 95% CI -0.29 to 0.12; P = 0.42). Sensitivity analyses were conducted to separately analyze depression (n = 5) and mood (n = 2) outcomes; statins were associated with statistically significant improvements in mood scores (SMD = -0.43, 95% CI -0.61 to -0.24). Conclusions: Our findings refute evidence of negative effects of statins on psychological outcomes, providing some support for mood-related benefits. Future studies could examine the effects of statins in depressed populations.
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| 6. |
- Politis, Marios, et al.
(author)
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Clinical application of stem cell therapy in Parkinson's disease
- 2012
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 10
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Research review (peer-reviewed)abstract
- Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce longlasting symptomatic relief without side effects while counteracting PD progression.
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| 7. |
- Rohrmann, Sabine, et al.
(author)
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Meat consumption and mortality : results from the European Prospective Investigation into Cancer and Nutrition
- 2013
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 11, s. 63-
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Journal article (peer-reviewed)abstract
- Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality.Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality.Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
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| 8. |
- Timpka, Simon, et al.
(author)
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Muscle strength in adolescent men and risk of cardiovascular disease events and mortality in middle age: a prospective cohort study
- 2014
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 12:1
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Journal article (peer-reviewed)abstract
- Background Ischemic heart disease and stroke are two severe types of cardiovascular disease (CVD), a major contributor to the global burden of disease. The preventive framework currently includes promotion of both adequate cardiorespiratory and muscular fitness. Although muscle fitness is established as an indicator of health, it is currently unknown whether muscle strength is associated with later CVD independently of cardiorespiratory fitness. Methods We studied 38,588 Swedish men who in 1969 to 1970 (typically aged 18 years) completed compulsory conscription. Using the mean standardized score of three isometric muscle strength tests performed at conscription (hand grip, elbow flexion and knee extension), we categorized the subjects into three groups with the 25th to 75th percentile defining the reference category. We followed the cohort until 2012 for diagnosed CVD events and mortality via national health care registers and the national cause of death register. To estimate hazard ratios (HR) for CVD events (coronary heart disease or stroke) and CVD mortality we used Cox proportional hazard models adjusted for body mass index, smoking, alcohol consumption, cardiorespiratory fitness and socioeconomic status. Results Men with high muscle strength in adolescence had a decreased risk of later CVD events (HR 0.88, 95% confidence interval 0.77 to 0.99), whereas we observed no increased risk in men with low muscle strength (0.99, 0.86 to 1.13). However, low muscle strength was associated with increased risk of CVD mortality during middle age (1.31, 1.02 to 1.67). Conclusions Muscle strength in adolescent men is inversely associated with later CVD events and CVD mortality in middle age, independently of cardiorespiratory fitness and other important confounders. Thus, the role of muscle fitness in the prevention and pathogenesis of CVD warrants increased attention.
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| 9. |
- Vickers, Andrew J., et al.
(author)
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Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen
- 2014
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 12
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Journal article (peer-reviewed)abstract
- Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA. Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162). Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality. Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening.
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| 10. |
- Jiménez-Pavón, David, et al.
(author)
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Physical activity and clustered cardiovascular disease risk factors in young children : a cross-sectional study (the IDEFICS study)
- 2013
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In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 11
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Journal article (peer-reviewed)abstract
- BACKGROUND: The relevance of physical activity (PA) for combating cardiovascular disease (CVD) risk in children has been highlighted, but to date there has been no large-scale study analyzing that association in children aged ≤9 years of age. This study sought to evaluate the associations between objectively-measured PA and clustered CVD risk factors in a large sample of European children, and to provide evidence for gender-specific recommendations of PA.METHODS: Cross-sectional data from a longitudinal study in 16,224 children aged 2 to 9 were collected. Of these, 3,120 (1,016 between 2 to 6 years, 2,104 between 6 to 9 years) had sufficient data for inclusion in the current analyses. Two different age-specific and gender-specific clustered CVD risk scores associated with PA were determined. First, a CVD risk factor (CRF) continuous score was computed using the following variables: systolic blood pressure (SBP), total triglycerides (TG), total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c) ratio, homeostasis model assessment of insulin resistance (HOMA-IR), and sum of two skinfolds (score CRFs). Secondly, another CVD risk score was obtained for older children containing the score CRFs + the cardiorespiratory fitness variable (termed score CRFs + fit). Data used in the current analysis were derived from the IDEFICS ('Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS') study.RESULTS: In boys <6 years, the odds ratios (OR) for CVD risk were elevated in the least active quintile of PA (OR: 2.58) compared with the most active quintile as well as the second quintile for vigorous PA (OR: 2.91). Compared with the most active quintile, older children in the first, second and third quintiles had OR for CVD risk score CRFs + fit ranging from OR 2.69 to 5.40 in boys, and from OR 2.85 to 7.05 in girls.CONCLUSIONS: PA is important to protect against clustering of CVD risk factors in young children, being more consistent in those older than 6 years. Healthcare professionals should recommend around 60 and 85 min/day of moderate-to-vigorous PA, including 20 min/day of vigorous PA.Please see related commentary: http://www.biomedcentral.com/1741-7015/11/173.
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