Associations between fruit and vegetable intake, leisure-time physical activity, sitting time and self-rated health among older adults : cross-sectional data from the WELL study

BackgroundLifestyle behaviours, such as healthy diet, physical activity and sedentary behaviour, are key elements of healthy ageing and important modifiable risk factors in the prevention of chronic diseases. Little is known about the relationship between these behaviours in older adults. The purpose of this study was to explore the relationship between fruit and vegetable (F&V) intake, leisure-time physical activity (LTPA) and sitting time (ST), and their association with self-rated health in older adults.MethodsThis cross-sectional study comprised 3,644 older adults (48% men) aged 55-65 years, who participated in the Wellbeing, Eating and Exercise for a Long Life ("WELL") study. Respondents completed a postal survey about their health and their eating and physical activity behaviours in 2010 (38% response rate). Spearman\u27s coefficient (rho) was used to evaluate the relationship between F&V intake, LTPA and ST. Their individual and shared associations with self-rated health were examined using ordinal logistic regression models, stratified by sex and adjusted for confounders (BMI, smoking, long-term illness and socio-demographic characteristics).ResultsThe correlations between F&V intake, LTPA and ST were low. F&V intake and LTPA were positively associated with self-rated health. Each additional serving of F&V or MET-hour of LTPA were associated with approximately 10% higher likelihood of reporting health as good or better among women and men. The association between ST and self-rated health was not significant in the multivariate analysis. A significant interaction was found (ST*F&V intake). The effect of F&V intake on self-rated health increased with increasing ST in women, whereas the effect decreased with increasing ST in men.ConclusionThis study contributes to the scarce literature related to lifestyle behaviours and their association with health indicators among older adults. The findings suggest that a modest increase in F&V intake, or LTPA could have a marked effect on the health of older adults. Further research is needed to fully understand the correlates and determinants of lifestyle behaviours, particularly sitting time, in this age group

The influence of glucose-lowering therapies on cancer risk in type 2 diabetes

AIMS/HYPOTHESIS: The risk of developing a range of solid tumours is increased in type 2 diabetes, and may be influenced by glucose-lowering therapies. We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues. METHODS: This was a retrospective cohort study of people treated in UK general practices. Those included in the analysis developed diabetes >40 years of age, and started treatment with oral agents or insulin after 2000. A total of 62,809 patients were divided into four groups according to whether they received monotherapy with metformin or sulfonylurea, combined therapy (metformin plus sulfonylurea), or insulin. Insulin users were grouped according to treatment with insulin glargine, long-acting human insulin, biphasic analogue and human biphasic insulin. The outcome measures were progression to any solid tumour, or cancer of the breast, colon, pancreas or prostate. Confounding factors were accounted for using Cox proportional hazards models. RESULTS: Metformin monotherapy carried the lowest risk of cancer. In comparison, the adjusted HR was 1.08 (95% CI 0.96-1.21) for metformin plus sulfonylurea, 1.36 (95% CI 1.19-1.54) for sulfonylurea monotherapy, and 1.42 (95% CI 1.27-1.60) for insulin-based regimens. Adding metformin to insulin reduced progression to cancer (HR 0.54, 95% CI 0.43-0.66). The risk for those on basal human insulin alone vs insulin glargine alone was 1.24 (95% CI 0.90-1.70). Compared with metformin, insulin therapy increased the risk of colorectal (HR 1.69, 95% CI 1.23-2.33) or pancreatic cancer (HR 4.63, 95% CI 2.64-8.10), but did not influence the risk of breast or prostate cancer. Sulfonylureas were associated with a similar pattern of risk as insulin. CONCLUSIONS/INTERPRETATION: Those on insulin or insulin secretagogues were more likely to develop solid cancers than those on metformin, and combination with metformin abolished most of this excess risk. Metformin use was associated with lower risk of cancer of the colon or pancreas, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk as compared with human insulin

LDL-cholesterol concentrations: a genome-wide association study

BACKGROUND: LDL cholesterol has a causal role in the development of cardiovascular disease. Improved understanding of the biological mechanisms that underlie the metabolism and regulation of LDL cholesterol might help to identify novel therapeutic targets. We therefore did a genome-wide association study of LDL-cholesterol concentrations. METHODS: We used genome-wide association data from up to 11,685 participants with measures of circulating LDL-cholesterol concentrations across five studies, including data for 293 461 autosomal single nucleotide polymorphisms (SNPs) with a minor allele frequency of 5% or more that passed our quality control criteria. We also used data from a second genome-wide array in up to 4337 participants from three of these five studies, with data for 290,140 SNPs. We did replication studies in two independent populations consisting of up to 4979 participants. Statistical approaches, including meta-analysis and linkage disequilibrium plots, were used to refine association signals; we analysed pooled data from all seven populations to determine the effect of each SNP on variations in circulating LDL-cholesterol concentrations. FINDINGS: In our initial scan, we found two SNPs (rs599839 [p=1.7x10(-15)] and rs4970834 [p=3.0x10(-11)]) that showed genome-wide statistical association with LDL cholesterol at chromosomal locus 1p13.3. The second genome screen found a third statistically associated SNP at the same locus (rs646776 [p=4.3x10(-9)]). Meta-analysis of data from all studies showed an association of SNPs rs599839 (combined p=1.2x10(-33)) and rs646776 (p=4.8x10(-20)) with LDL-cholesterol concentrations. SNPs rs599839 and rs646776 both explained around 1% of the variation in circulating LDL-cholesterol concentrations and were associated with about 15% of an SD change in LDL cholesterol per allele, assuming an SD of 1 mmol/L. INTERPRETATION: We found evidence for a novel locus for LDL cholesterol on chromosome 1p13.3. These results potentially provide insight into the biological mechanisms that underlie the regulation of LDL cholesterol and might help in the discovery of novel therapeutic targets for cardiovascular disease

Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients

<p>Abstract</p> <p>Background</p> <p>Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic.</p> <p>Methods</p> <p>Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed.</p> <p>Results</p> <p>The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine.</p> <p>Conclusion</p> <p>Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.</p

The outcome of trachomatous trichiasis surgery in Ethiopia: risk factors for recurrence.

BACKGROUND: Over 1.2 million people are blind from trachomatous trichiasis (TT). Lid rotation surgery is the mainstay of treatment, but recurrence rates can be high. We investigated the outcomes (recurrence rates and other complications) of posterior lamellar tarsal rotation (PLTR) surgery, one of the two most widely practised TT procedures in endemic settings. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a two-year follow-up study of 1300 participants who had PLTR surgery, conducted by one of five TT nurse surgeons. None had previously undergone TT surgery. All participants received a detailed trachoma eye examination at baseline and 6, 12, 18 and 24 months post-operatively. The study investigated the recurrence rates, other complications and factors associated with recurrence. Recurrence occurred in 207/635 (32.6%) and 108/641 (16.9%) of participants with pre-operative major (>5 trichiatic lashes) and minor (5 lashes (major recurrence). Recurrence was greatest in the first six months after surgery: 172 cases (55%) occurring in this period. Recurrence was associated with major TT pre-operatively (OR 2.39, 95% CI 1.83-3.11), pre-operative entropic lashes compared to misdirected/metaplastic lashes (OR 1.99, 95% CI 1.23-3.20), age over 40 years (OR 1.59, 95% CI 1.14-2.20) and specific surgeons (surgeon recurrence risk range: 18%-53%). Granuloma occurred in 69 (5.7%) and notching in 156 (13.0%). CONCLUSIONS/SIGNIFICANCE: Risk of recurrence is high despite high volume, highly trained surgeons. However, the vast majority are minor recurrences, which may not have significant corneal or visual consequences. Inter-surgeon variation in recurrence is concerning; surgical technique, training and immediate post-operative lid position require further investigation

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA(1c) levels.RESEARCH DESIGN AND METHODS-We studied associations with HbA(1c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA(1c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.RESULTS-Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10(-26)), HFE (rs1800562/P = 2.6 x 10(-20)), TMPRSS6 (rs855791/P = 2.7 x 10(-14)), ANK1 (rs4737009/P = 6.1 x 10(-12)), SPTA1 (rs2779116/P = 2.8 x 10(-9)) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10(-9)), and four known HbA(1c) loci: HK1 (rs16926246/P = 3.1 x 10(-54)), MTNR1B (rs1387153/P = 4.0 X 10(-11)), GCK (rs1799884/P = 1.5 x 10(-20)) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10(-18)). We show that associations with HbA(1c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (%HbA(1c)) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA(1c).CONCLUSIONS-GWAS identified 10 genetic loci reproducibly associated with HbA(1c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA(1c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA(1c) Diabetes 59: 3229-3239, 201

Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye

Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level