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Sample records for age-related risk factors

  1. Risk Factors for Age-Related Maculopathy

    PubMed Central

    Connell, Paul P.; Keane, Pearse A.; O'Neill, Evelyn C.; Altaie, Rasha W.; Loane, Edward; Neelam, Kumari; Nolan, John M.; Beatty, Stephen

    2009-01-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition. PMID:20339564

  2. Genetic risk factors and age-related macular degeneration (AMD)

    PubMed Central

    Mousavi, Maryam; Armstrong, Richard A.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available.

  3. Modifiable risk factors for age-related macular degeneration.

    PubMed

    Guymer, Robyn H; Chong, Elaine Wei-Tinn

    2006-05-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in Australia and other Western countries. As there is no cure for AMD, and treatments to stop its progression have met with limited success, there is an interest in identifying modifiable risk factors to prevent or slow disease progression. To date, smoking is the only proven modifiable risk factor for AMD. Other factors under study include (i) cardiovascular risk factors such as hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors including fat and antioxidant intake, but so far these studies have produced conflicting results. Dietary fat in relation to AMD has recently attracted media attention. Despite very limited work supporting an association between vegetable fat and AMD, widespread publicity advocating margarine as a cause of AMD and encouraging use of butter instead has caused confusion and anxiety among sufferers of AMD and the general public, as well as concern among health professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark green or yellow vegetables exist in high concentrations in the macula and are hypothesised to play a protective role. Of nine controlled trials of supplementation with carotenoids and other antioxidants, three suggested that various combinations of antioxidants and carotenoids were protective. While a low-fat diet rich in dark green and yellow vegetables is advocated in general, any specific recommendations regarding certain fats or antioxidant supplementation and AMD are not based on consistent findings at this stage. PMID:16646746

  4. Nutritional Risk Factors for Age-Related Macular Degeneration

    PubMed Central

    Ersoy, Lebriz; Lechanteur, Yara T.; Hoyng, Carel B.; Kirchhof, Bernd; den Hollander, Anneke I.

    2014-01-01

    Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD cases and 1773 controls from the European Genetic Database. Serum levels of lipids and lipoproteins were determined. The relationship between nutritional factors and late AMD was assessed using logistic regression. Based on multivariate analysis, area-under-the-curve (AUC) was calculated by receiver-operating-characteristics (ROC). Results. In a multivariate analysis, besides age and smoking, obesity (odds ratio (OR): 1.44, P = 0.014) and red meat intake (daily: OR: 2.34, P = 8.22 × 10−6; 2–6x/week: OR: 1.67, P = 7.98 × 10−5) were identified as risk factors for developing late AMD. Fruit intake showed a protective effect (daily: OR: 0.52, P = 0.005; 2–6x/week: OR: 0.58, P = 0.035). Serum lipid and lipoprotein levels showed no significant association with late AMD. ROC for nutritional factors, smoking, age, and BMI revealed an AUC of 0.781. Conclusion. Red meat intake and obesity were independently associated with increased risk for late AMD, whereas fruit intake was protective. A better understanding of nutritional risk factors is necessary for the prevention of AMD. PMID:25101280

  5. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    PubMed Central

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  6. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    MedlinePlus

    ... for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  7. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment.

    PubMed

    Nolan, John M; Stack, Jim; O' Donovan, Orla; Loane, Edward; Beatty, Stephen

    2007-01-01

    Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM). This study was undertaken to investigate MP optical density with respect to risk factors for ARM, in 828 healthy subjects from an Irish population. MP optical density was measured psychophysically using heterochromatic flicker photometry, serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed using a validated food-frequency questionnaire. Clinical and personal details were also recorded, with particular attention directed towards risk factors for ARM. We report a statistically significant age-related decline in MP optical density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical density than never smokers and this difference was statistically significant (p<0.01). Subjects with a confirmed family history of ARM had significantly lower levels of MP optical density than subjects with no known family history of disease (p<0.01). For each of these established risk factors, their statistically significant negative association with MP persisted after controlling for the other two, and also after controlling for other potentially confounding variables such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal pathology, and in advance of disease onset, the relative lack of MP seen in association with increasing age, tobacco use and family history of ARM supports the hypothesis that the enhanced risk that these variables represent for ARM may be attributable, at least in part, to a parallel deficiency of macular carotenoids. PMID:17083932

  8. Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

  9. Strength training in the elderly: effects on risk factors for age-related diseases.

    PubMed

    Hurley, B F; Roth, S M

    2000-10-01

    Strength training (ST) is considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure that is associated with advanced age. This reversal is thought to result in improvements in functional abilities and health status in the elderly by increasing muscle mass, strength and power and by increasing bone mineral density (BMD). In the past couple of decades, many studies have examined the effects of ST on risk factors for age-related diseases or disabilities. Collectively, these studies indicate that ST in the elderly: (i) is an effective intervention against sarcopenia because it produces substantial increases in the strength, mass, power and quality of skeletal muscle; (ii) can increase endurance performance; (iii) normalises blood pressure in those with high normal values; (iv) reduces insulin resistance; (v) decreases both total and intra-abdominal fat; (vi) increases resting metabolic rate in older men; (vii) prevents the loss of BMD with age; (viii) reduces risk factors for falls; and (ix) may reduce pain and improve function in those with osteoarthritis in the knee region. However, contrary to popular belief, ST does not increase maximal oxygen uptake beyond normal variations, improve lipoprotein or lipid profiles, or improve flexibility in the elderly. PMID:11048773

  10. Increased Waist-to-height Ratio May Contribute to Age-related Increase in Cardiovascular Risk Factors

    PubMed Central

    Akhlaghi, Masoumeh; Kamali, Majid; Dastsouz, Farideh; Sadeghi, Fatemeh; Amanat, Sassan

    2016-01-01

    Background: The risk of cardiovascular diseases (CVDs) increases with age. The objective was to determine whether lifestyle and dietary behaviors and anthropometric measures, which are affected by these behaviors, contribute to the increase of CVD risk factors across age categories of 20–50-year-old. Methods: In a cross-sectional design, 437 adults aged 20–50-year-old were selected from households living in Shiraz. Risk factors of CVD, including body mass index (BMI), waist-to-height ratio (WHtR), blood pressure, fasting blood glucose (FBG), serum triglycerides, total cholesterol, and low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) as well as lifestyle behaviors (physical activity and smoking), dietary habits, and food intakes were assessed across the age categories of 20–29, 30–39, and 40–50 years. Linear regression was used to examine the contribution of different variables to the age-related increase of CVD risk factors. Results: All CVD risk factors, except for HDL-C, significantly increased across age categories. Older subjects had healthier dietary habits and food intakes, but they possessed nonsignificantly lower physical activity and higher smoking rate compared to younger adults. Adjusting for physical activity, smoking, and BMI did not change the significant positive association between age and CVD risk factors but adjusting for WHtR disappeared associations for blood pressure, triglycerides, and metabolic syndrome although significant associations remained for FBG and total and LDL-C. Conclusions: Age-related increase of CVD risk factors occurred independent of lifestyle habits. WHtR, but not BMI, may partially contribute to the age-related increase in CVD risk factors. PMID:27195100

  11. Diabetes and Age-Related Demographic Differences in Risk Factor Control

    PubMed Central

    Egan, Brent M.; Li, Jiexiang; Wolfman, Tamara E.; Sinopoli, Angelo

    2014-01-01

    Background Disparate vascular outcomes in diabetes by race/ethnicity may reflect differential risk factor control, especially pre-Medicare. Methods Assess concurrent target attainment for glycohemoglobin <7%, non-HDL-cholesterol <130 mg/dL, and blood pressure <140/<90 mmHg in white, black, and Hispanic diabetics <65 (younger) and ≥65 (older) years. NHANES 1999–2010 data were analyzed on diagnosed and undiagnosed diabetics ≥18 years. Results Concurrent target attainment was higher in whites (18.7%) than blacks (13.4% [p=0.02] and Hispanics (10.3%, p<0.001) <65 but not ≥65 years (20.0% vs. 15.9% [p=0.13], 19.5% [p=0.88]). Disparities in healthcare insurance among younger whites, blacks, and Hispanics, respectively, (87.4% vs. 81.1% (p<0.01), 68.0% (p<0.001) and infrequent healthcare (0–1 visits/year; 14.3% vs. 15.0% (p=NS), 32.0% (p<0.001) declined with age. Cholesterol treatment predicted concurrent control in both age groups (multivariable odds ratio >2, p<0.001). Risk factor awareness and treatment were lower in Hispanics than whites. When treated, diabetes and hypertension control were greater in whites than blacks or Hispanics. Conclusions Concurrent risk factor control is low in all diabetics and could improve with greater statin use. Insuring younger adults, especially Hispanic, could raise risk factor awareness and treatment. Improving treatment effectiveness in younger black and Hispanic diabetics could promote equitable risk factor control. PMID:24952652

  12. Associations between Genetic Polymorphisms of Insulin-like Growth Factor Axis Genes and Risk for Age-Related Macular Degeneration

    PubMed Central

    Chiu, Chung-Jung; Conley, Yvette P.; Gorin, Michael B.; Gensler, Gary; Lai, Chao-Qiang; Shang, Fu; Taylor, Allen

    2011-01-01

    Purpose. To investigate whether insulin-like growth factor (IGF) axis genes, together with a novel dietary risk factor, the dietary glycemic index (dGI), and body mass index (BMI) affect the risk for age-related macular degeneration (AMD). Methods. This case–control study involved 962 subjects originally recruited through the Age-Related Eye Disease Study (AREDS) Genetic Repository. After those with missing covariates or invalid calorie intake (n = 23), diabetes (n = 59), and non-Caucasian race (n = 16) were excluded, 864 participants were used, including 209 AREDS category 1 participants (control group), 354 category 2 or 3 participants (drusen group), and 301 category 4 participants (advanced AMD group). A total of 25 single-nucleotide polymorphisms (SNPs) selected from IGF-1 (n = 9), IGF-2 (n = 1), IGF binding protein 1 (IGFBP1; n = 3), IGFBP3 (n = 3), acid-labile subunit of IGFBP (IGFALS; n = 2), IGF1 receptor (IGF1R; n = 4), and IGF2R (n = 3) were genotyped. SNP-AMD associations were measured with genotype, allele χ2 tests and Armitage's trend test. Odds ratios (OR), 95% confidence intervals (CIs), and SNP-exposure interactions were evaluated by multivariate logistic regression. Results. One SNP (rs2872060) in IGF1R revealed a significant association with advanced AMD (P-allele = 0.0009, P-trend = 0.0008; the significance level was set at 0.05/25 = 0.002 for multiple comparisons). The risk allele (G) in the heterozygous and homozygous states (OR, 1.67 and 2.93; 95% CI, 1.03–2.71 and 1.60–5.36, respectively) suggests susceptibility and an additive effect on AMD risk. Further stratification analysis remained significant for both neovascularization (OR, 1.49 and 2.61; 95% CI, 0.90–2.48 and 1.39–4.90, respectively) and geographic atrophy (OR, 2.57 and 4.52; 95% CI, 0.99–6.71 and 1.49–13.74, respectively). The G allele interaction analysis with BMI was significant for neovascularization (P = 0.042) but not for geographic atrophy (P = 0.47). No

  13. Metabolic risk factors, coping with stress, and psychological well-being in patients with age-related macular degeneration.

    PubMed

    Cavar, Ivan; Lovrić, Sanjin; Vukojević, Mladenka; Sesar, Irena; Petric-Vicković, Ivanka; Sesar, Antonio

    2014-03-01

    The aim of this study was to determine the relationship between the risk factors (age, obesity, hypertension, hyperlipidemia, smoking, consumption of alchohol and drugs, positive family history, and exposure to sunlight), coping with stress, psychological well-being and age-related macular degeneration (ARMD). Forty patients with ARMD (case group) and 63 presbyopes (control group) participated in the study. Patient data were collected through general information questionnaire including patient habits, the COPE questionnaire that showed the way the patients handling stress, and the GHQ that analyzed the psychological aspects of their quality of life. These questionnaires were administered to the patients during ophthalmologic examination. The study involved 46 (44.66%) men and 57 (55.33%) women. Statistical analysis showed that the major risks for the development of ARMD were elevated cholesterol, triglycerides and LDL cholesterol in plasma. A significantly higher number ofARMD patients had a positive family history when compared with presbyopes. This study showed presbyopes to cope with emotional problems significantly better and to have a lower level of social dysfunction when compared with ARMD patients. However, it is necessary to conduct further studies in a large number of patients to determine more accurately the pathophysiological mechanisms of metabolic factors as well as the impact of the disease on the quality of life in patients with ARMD. PMID:24974669

  14. The prevalence and risk factors for age-related macular degeneration in rural-urban India, Sankara Nethralaya Rural-Urban Age-related Macular degeneration study, Report No. 1.

    PubMed

    Raman, R; Pal, S S; Ganesan, S; Gella, L; Vaitheeswaran, K; Sharma, T

    2016-05-01

    PurposeTo report the age- and gender-adjusted prevalence rates of early and late age-related maculopathy (ARM) and associated risk factors in rural and urban Indian population.MethodsA population-based cross-sectional study was carried out in South India between 2009 and 2011. Of the 6617 subjects ≥60 years enumerated ones, 5495 (83.04%) participated in the eye examination. A detailed history including data on demographic, socioeconomic, and ocular history was obtained. Participants underwent detailed ophthalmic evaluation including 30° 3-field photograph as per Age-Related Eye Disease Study protocol. The ARM was graded according to the International ARM Epidemiological Study Group.ResultsAge- and gender-adjusted prevalence of early ARM was 20.91% (20.86-20.94) in the rural population and 16.37% (16.32-16.42) in the urban population. Similarly, the prevalence of late ARM was 2.26% (2.24-2.29) and 2.32% (2.29-2.34) in the rural and urban population, respectively. In both rural and urban populations, risk factors that were related to both early and late ARM were age, per year increase (OR, range 1.00-1.08); middle socioeconomic status (OR, range 1.05-1.83); and smokeless tobacco (OR, range 1.11-2.21). Protective factor in both was the presence of diabetes mellitus in all ARM (OR, range 0.34-0.83). Risk factors, only in the rural arm, were female gender (OR, range 1.06-1.64), past smoker (OR, 1.14), and serum low-density lipoprotein cholesterol level (OR, 1.03).ConclusionsThe study reports smokessless tobacco as a risk factor for both early and late ARM and identified a higher prevalence of early ARM in the rural population compared with urban population. PMID:26915746

  15. Complement factor H Val62Ile variant and risk of age-related macular degeneration: A meta-analysis

    PubMed Central

    Yuan, Dongqing; Yang, Qin; Liu, Xiaoyi; Yuan, Donglan; Yuan, Songtao; Xie, Ping

    2013-01-01

    Purpose To evaluate the precise association of complement factor H (CFH) Val62Ile polymorphism with age-related macular degeneration (AMD) susceptibility. Methods We performed a meta-analysis using databases including PubMed, EMBASE, and Web of Science to find relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effect and random-effects models. The inconsistency index (I2) was used to assess heterogeneity. Funnel plots and Egger’s test were used to evaluate publication bias. Sensitivity analysis was also performed. Results Fourteen studies including 4,438 patients with AMD and 6,099 controls based on the search criteria were involved in the meta-analysis. In overall populations, the pooled OR1 for genotype GA+GG versus homozygous genotype AA was 2.28 (95% confidence interval (CI): 1.48–3.52), the OR2 of heterozygous genotype GA versus AA was 1.58 (95% CI: 1.13–2.19), the OR3 of homozygous genotype GG versus AA was 2.90 (95% CI: 1.95–4.30), and the OR4 of allele G versus A was 1.77 (95% CI: 1.43–2.21). In Asian populations, our results provided substantial evidence that the Val62Ile variant was significantly associated with AMD (OR4=1.85, 95% CI: 1.63–2.09). However, in Caucasian populations, no significant association of Val62Ile with AMD was established in all circumstances. Conclusions Our analysis provides substantial evidence that the Val62Ile variant is significantly associated with AMD in Asian populations. However, our results have demonstrated no link between the Val62Ile polymorphism and AMD in Caucasian populations. PMID:23441108

  16. Physical, Heritable and Age-Related Factors as Modifiers of Radiation Cancer Risk in Patched Heterozygous Mice

    SciTech Connect

    Pazzaglia, Simonetta Pasquali, Emanuela M.Sc.; Tanori, Mirella; Mancuso, Mariateresa; Leonardi, Simona; Di Majo, Vincenzo; Rebessi, Simonetta; Saran, Anna

    2009-03-15

    Purpose: To address the tumorigenic potential of exposure to low/intermediate doses of ionizing radiation and to identify biological factors influencing tumor response in a mouse model highly susceptible to radiogenic cancer. Methods and Materials: Newborn Ptc1 heterozygous mice were exposed to X-ray doses of 100, 250, and 500 mGy, and tumor development was monitored for their lifetime. Additional groups were irradiated with the same doses and sacrificed at fixed times for determination of short-term endpoints, such as apoptosis and early preneoplastic lesions in cerebellum. Finally, groups of Ptc1 heterozygous mice were bred on the C57BL/6 background to study the influence of common variant genes on radiation response. Results: We have identified a significant effect of low-intermediate doses of radiation (250 and 500 mGy) in shortening mean survival and inducing early and more progressed stages of tumor development in the cerebellum of Ptc1{sup +/-} mice. In addition, we show that age at exposure and heritable factors are potent modifiers of radiation-related cancer risk. Conclusions: The Ptc1 knockout mouse model offers a highly sensitive system that may potentially help to improve understanding and quantification of risk at low doses, such as doses experienced in occupational and medical exposures, and clarify the complex interactions between genetic and environmental factors underlying cancer susceptibility.

  17. Risk Factors for Four-Year Incidence and Progression of Age-Related Macular Degeneration: The Los Angeles Latino Eye Study

    PubMed Central

    CHOUDHURY, FARZANA; VARMA, ROHIT; MCKEAN-COWDIN, ROBERTA; KLEIN, RONALD; AZEN, STANLEY P.

    2011-01-01

    PURPOSE To identify risk factors for 4-year incidence and progression of age-related macular degeneration (AMD) in adult Latinos. DESIGN Population-based prospective cohort study. METHODS Participants, aged 40 or older, from The Los Angeles Latino Eye Study (LALES) underwent standardized comprehensive ophthalmologic examinations at baseline and at 4 years of follow-up. Age-related macular degeneration was detected by grading 30-degree stereoscopic fundus photographs using the modified Wisconsin Age-Related Maculopathy Grading System. Multivariate stepwise logistic regression was used to examine the independent association of incidence and progression of AMD and baseline sociodemographic, behavioral, clinical, and ocular characteristics. RESULTS Multivariate analyses revealed that older age (OR per decade of age: 1.52; 95% CI: 1.29, 1.85) and higher pulse pressure (OR per 10 mm Hg: 2.54; 95% CI: 1.36, 4.76) were independently associated with the incidence of any AMD. The same factors were associated with early AMD, soft indistinct drusen, and retinal pigmentary abnormalities. Additionally, presence of clinically diagnosed diabetes mellitus was independently associated with increased retinal pigment (OR: 1.66; 95% CI: 1.01, 2.85), and male gender was associated with retinal pigment epithelial depigmentation (OR 2.50; 95% CI: 1.48, 4.23). Older age (OR per decade of age: 2.20; 95% CI: 1.82, 2.67) and current smoking (OR: 2.85; 95% CI: 1.66, 4.90) were independently associated with progression of AMD. CONCLUSIONS Several modifiable risk factors were associated with 4-year incidence and progression of AMD in Latinos. The results suggest that interventions aimed at reducing pulse pressure and promoting smoking cessation may reduce incidence and progression of AMD, respectively. PMID:21679916

  18. Effect of High-Density Lipoprotein Metabolic Pathway Gene Variations and Risk Factors on Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in China

    PubMed Central

    Sun, Yaoyao; Bai, Yujing; Wang, Bin; Yu, Wenzhen; Zhao, Mingwei; Li, Xiaoxin

    2015-01-01

    Purpose To investigate the effect of genetic variants in the high-density lipoprotein (HDL) metabolic pathway and risk factors on neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in China. Methods A total of 742 Chinese subjects, including 221 controls, 230 cases with nAMD, and 291 cases with PCV, were included in the present study. Five single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway (HDLMP) including cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC) and lipoprotein lipase (LPL) were genotyped in all study subjects with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Risk factors including gender, hypertension, hyperlipidemia, diabetes mellitus, and coronary artery disease were identified. Chi-square tests or Fisher’s exact tests were applied to discover associations between SNPs and risk factors for PCV and nAMD. Gene-gene interactions and gene-environment interactions were evaluated by the multifactor-dimensionality reduction (MDR) method. Results CETP rs3764261 were significantly associated with an increased risk for PCV (odds ratio (OR) = 1.444, P = 0.0247). LIPC rs1532085 conferred an increased risk for PCV (OR = 1.393, P = 0.0094). We found no association between PCV and LPL rs12678919, LIPC rs10468017 or CETP rs173539. No association was found between five SNPs with nAMD. Regarding risk factors, females were found to have significantly decreased risks for both PCV and nAMD (P = 0.006 and 0.001, respectively). Coronary artery disease (CAD) was a risk factor in PCV patients but played a protective role in nAMD patients. Hyperlipidemia was associated with PCV but not with nAMD. Neither hypertension nor diabetes mellitus was associated with PCV or nAMD. The MDR analysis revealed that a three-locus model with rs12678919, rs1532085, and gender was the best model for nAMD, while a five-locus model consisting of rs

  19. Age-related percutaneous penetration part 1: skin factors.

    PubMed

    Konda, S; Meier-Davis, S R; Cayme, B; Shudo, J; Maibach, H I

    2012-05-01

    Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration. PMID:22622279

  20. Cross Sectional and Longitudinal Associations between Cardiovascular Risk Factors and Age Related Macular Degeneration in the EPIC-Norfolk Eye Study

    PubMed Central

    Yip, Jennifer L. Y.; Khawaja, Anthony P.; Chan, Michelle P. Y.; Broadway, David C.; Peto, Tunde; Tufail, Adnan; Luben, Robert; Hayat, Shabina; Bhaniani, Amit; Wareham, Nicholas J.; Khaw, Kay-Tee; Foster, Paul J.

    2015-01-01

    Purpose To examine the cross sectional and longitudinal relationship between cardiovascular risk factors and age-related macular degeneration (AMD) in a large British cohort study. Methods The EPIC Norfolk Eye study is nested in a larger prospective cohort study. Data on cardiovascular risk factors were collected at baseline (1993-1997) and follow up (2006-2011) via clinical examination, validated lifestyle questionnaires and serum blood samples. AMD was ascertained using standardised grading of fundus photographs at the follow up. Logistic regression was used to examine associations between baseline and follow up risk factors with AMD. Results 5,344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD in participants with mean age of 67.4 years old (range 44-91) at diagnosis. There were 28 cases of late AMD (0.5%, 95% confidence interval (CI)=0.3-0.8%) and 645 cases of early AMD (12.1%, 95%CI=11.2-13.0.%). In multivariable analysis, older people with higher levels of baseline high density lipoprotein- cholesterol (HDL-C ) and C-reactive protein (CRP) were more likely to have any signs of AMD, after adjusting for sex, education, smoking, and systolic blood pressure. In cross sectional analysis, only older age and higher HDL were significantly associated with AMD. Conclusions We have found that older age and higher levels of CRP and HDL-C were associated with increased odds of AMD in this population in the longitudinal analysis, but older age and HDL-C, not CRP was significantly associated with AMD in the cross sectional analysis. The prevalence of AMD in this cohort was low compared to other cohorts in Europe, the US and Australia, and probably reflects the some selection biases in follow up participation as well as the low rate of smoking among our healthy participants. PMID:26176222

  1. A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

    NASA Astrophysics Data System (ADS)

    Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

    2016-05-01

    The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

  2. Complement factor H polymorphism and age-related macular degeneration.

    PubMed

    Edwards, Albert O; Ritter, Robert; Abel, Kenneth J; Manning, Alisa; Panhuysen, Carolien; Farrer, Lindsay A

    2005-04-15

    Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association (P = 4.95 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD. PMID:15761121

  3. Sun exposure and visual field damage among children on the Adriatic Island Rab--possible initial risk factor in development of age-related macular degeneration.

    PubMed

    Vojniković, Bozidar; Micović, Vladimir; Coklo, Miran; Vojniković, Davor

    2009-09-01

    The Adriatic Island Rab, situated in the northern part of the Croatian sea, is more strongly exposed to sunlight (especially from May to October) than the other parts of Croatia and most of the European countries. As consequences of higher solar radiation, significant percentage of Pseudoexfoliation of lens capsula occurs in 15% and fundus picture of AMD (Age-Related Macular Degeneration) in 18% of agriculturalists and fishermen (45-70 years old). We previously presented the first clinical study showing that in AMD the peripheral visual field is also damaged. In this clinical study we examined 68 children (8-15 years old), including following procedures: vision correction, slit lamp examination, visual field in technic of isopters and profile quantitative perimetry (meridian retinal thresholds examination) using Kowa automated perimeter. In 15% of examinees we found strictly foveal "degeneration", and changes of visual fields: higher meridian thresholds and typical changes with invagination of isopters. It is very interesting that these children with damaged visual field and fundus picture do not protect their eyes from the sunlight during summertime. We suggest the possibility of the influence of higher sun radiation as one of the risk factors in the earlier development of future AMD. PMID:19860099

  4. Complement Factor H Polymorphism in Age-Related Macular Degeneration

    PubMed Central

    Klein, Robert J.; Zeiss, Caroline; Chew, Emily Y.; Tsai, Jen-Yue; Sackler, Richard S.; Haynes, Chad; Henning, Alice K.; SanGiovanni, John Paul; Mane, Shrikant M.; Mayne, Susan T.; Bracken, Michael B.; Ferris, Frederick L.; Ott, Jurg; Barnstable, Colin; Hoh., Josephine

    2006-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10−7). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies. PMID:15761122

  5. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

    ... Issue Past Issues Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer ... learn more about the effects of sustained low-calorie diets in humans on factors affecting aging. This ...

  6. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    MedlinePlus

    ... macular degeneration Three studies point to same risk gene for age-related macular degeneration NIH-funded research ... in Nature Genetics have converged on the same gene as a rare, but powerful risk factor for ...

  7. Association between complement factor I gene polymorphisms and the risk of age-related macular degeneration: a Meta-analysis of literature

    PubMed Central

    Wang, Qin; Zhao, Hai-Sheng; Li, Li

    2016-01-01

    AIM To systematically review the association between complement factors I (CFI) polymorphisms and age-related macular degeneration (AMD) and to explore whether CFI polymorphisms are associated with AMD. METHODS Meta-analysis of articles published from 1995 to January 2015 of articles involved with AMD and polymorphisms of the CFI gene. Eligible data were pooled in a Meta-analysis, analyzing using STATA software (version 12.0), Review Manager (version 5.2) and different models based on the heterogeneity of effect sizes. Egger's test, Begg's rank correlation methods were used to evaluate for publication bias. RESULTS Thirteen articles were eligible, describing two loci polymorphisms of the CFI gene (of which 12 articles focus on rs10033900T>C and 3 articles focus on rs2285714C>T). For rs10033900T>C, the results of our study revealed that having a mutant allele C, TC, CC and TC+CC was associated with a decreased risk of AMD in all population groups studied (C versus T models, OR=0.84, 95%CI: 0.72-0.99, P=0.04; TC versus TT models OR=0.89, 95%CI: 0.88-0.99, P=0.04; CC versus TT models, OR=0.76, 95%CI: 0.60-0.98, P=0.03; TC+CC versus TT models, OR=0.81, 95%CI:0.65-0.99, P=0.04). We found that C allele were related to lower AMD risk in the Caucasian population by subgroup analysis, but there was no association with AMD under the allele and genotypes comparison in Asian studies. For rs2285714 C>T, the TC, TT genotypes contributed to a higher risk of AMD, compared with the CC carriers and TC+CC (OR=1.34, 95%CI: 1.09-1.63, P=0.004; OR=1.50, 95%CI: 1.25-1.80, P<0.0001). CONCLUSION This Meta-analysis suggests that CFI rs10033900T>C and rs2285714C>T polymorphisms may contribute to AMD. PMID:26949655

  8. Five-year incidence, progression and risk factors for age-related macular degeneration: The Age, Gene/Environment Susceptibility Study

    PubMed Central

    Jonasson, Fridbert; Fisher, Diana E.; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Klein, Ronald; Launer, Lenore J; Harris, Tamara; Gudnason, Vilmundur; Cotch, Mary Frances

    2014-01-01

    Objective To investigate the incidence and progression of age related m acular degeneration (AMD) and associated risk factors. Design Population-based prospective cohort study. Participants 2868 participants from the Age Gene/Environment Susceptibility-Reykjavik Study with retinal data at baseline and five-year follow-up. Methods Digital macular photographs were graded for presence of AMD. Participants completed a questionnaire and extensive clinical battery. Biomarkers were assessed. Risk factors for AMD were analyzed using multivariate regression analysis with odds ratios (ORs) and 95% confidence intervals (CIs). Main outcome measures AMD, defined as early or late. Results Among 2196 participants free of AMD at baseline, 14.9% developed incident AMD. In multivariate models, incident AMD was significantly associated with age (OR per year 1.14 (95% CI 1.11, 1.17)), current smoking (OR 2.07 (1.38, 3.11)), former smoking (OR 1.36 (1.04, 1.79)), plasma high-density lipoprotein (HDL) cholesterol level (OR 1.62 per mmol/L (1.19, 2.22)), and body mass index (BMI) (OR 1.04 per kg/m2 (1.01, 1.07)). Among 563 participants with early AMD at baseline, 22.7% progressed to late AMD (11.0% pure geographic atrophy (GA) and 11.7% exudative AMD). In multivariate analyses, age was significantly associated with progression to GA (OR 1.14 (1.07, 1.21)) and exudative AMD (OR 1.08 (1.01, 1.14)). Adjusting for age, female sex was associated with exudative AMD (OR 2.10 (1.10, 3.98)) and plasma HDL cholesterol with GA (OR 2.03 per mmol/L (1.02, 4.05)). Conclusion By age 85 years, 57.4% of participants had signs of AMD. Age, smoking, plasma HDL cholesterol, BMI and female sex are associated with AMD. Elevated HDL cholesterol is associated with GA development. PMID:24768241

  9. Low Calorie Diet Affects Aging-Related Factors

    MedlinePlus

    ... Research News From NIH Low Calorie Diet Affects Aging-Related Factors Past Issues / Summer 2006 Table of ... project sponsored by the NIH's National Institute on Aging (NIA) to learn more about the effects of ...

  10. Independent effects of age-related changes in waist circumference and BMI z scores in predicting cardiovascular disease risk factors in a prospective cohort of adolescent females

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Cross-sectional data indicate that central adiposity is associated with cardiovascular disease risk, independent of total adiposity. The use of longitudinal data to investigate the relation between changes in fat distribution and the emergence of risk factors is limited. OBJECTIVE: We ...

  11. Age-Related Factors in Second Language Acquisition.

    ERIC Educational Resources Information Center

    Twyford, Charles William

    The convergence of several lines of psycholinguistic and sociolinguistic research suggests possible explanations for age-related influences on language acquisition. These factors, which include cognitive development, sociocultural context, affective factors, and language input, can be helpful to language educators. By being alert to the cognitive…

  12. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  13. Age-Related Changes of Healthy Bone Marrow Cell Signaling in Response to Growth Factors Provide Insight into Low Risk MDS

    PubMed Central

    Kornblau, Steven M.; Cohen, Aileen C.; Soper, David; Huang, Ying-Wen; Cesano, Alessandra

    2016-01-01

    Background Single Cell Network Profiling (SCNP) is a multiparametric flow cytometry-based assay that quantifiably and simultaneously measures changes in intracellular signaling proteins in response to in vitro extracellular modulators at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder of hematopoietic stem cells that occurs in elderly subjects and is characterized by dysplasia and ineffective hematopoiesis. The functional responsiveness of MDS bone marrow (BM) hematopoietic cells, including functionally distinct myeloid and erythroid precursor subsets, to hematopoietic growth factors (HGF) and the relationship of modulated signaling to disease characteristics is poorly understood. Methods SCNP was used first to examine the effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34 expressing cell subsets in healthy BM (n=15). SCNP was then used to map functional signaling profiles in low risk (LR) MDS (n=7) for comparison to signaling in samples from healthy donors and to probe signaling associations within clinically defined subgroups. Results In healthy BM samples, signaling responses to HGF were quite homogeneous (i.e. tightly regulated) with age-dependent effects observed in response to EPO but not to GCSF. Despite the relatively small number of samples assayed in the study, LR MDS could be classified into distinct subgroups based on both cell subset frequency and signaling profiles. Conclusion As a correlate of underlying genetic abnormalities, signal transduction analyses may provide a functional and potentially clinically relevant classification of MDS. Further evaluation in a larger cohort is warranted. PMID:24106013

  14. The Application of Genetic Risk Scores in Age-Related Macular Degeneration: A Review

    PubMed Central

    Cooke Bailey, Jessica N.; Hoffman, Joshua D.; Sardell, Rebecca J.; Scott, William K.; Pericak-Vance, Margaret A.; Haines, Jonathan L.

    2016-01-01

    Age-related macular degeneration (AMD), a highly prevalent and impactful disease of aging, is inarguably influenced by complex interactions between genetic and environmental factors. Various risk scores have been tested that assess measurable genetic and environmental contributions to disease. We herein summarize and review the ability and utility of these numerous models for prediction of AMD and suggest additional risk factors to be incorporated into clinically useful predictive models of AMD. PMID:26959068

  15. The Application of Genetic Risk Scores in Age-Related Macular Degeneration: A Review.

    PubMed

    Cooke Bailey, Jessica N; Hoffman, Joshua D; Sardell, Rebecca J; Scott, William K; Pericak-Vance, Margaret A; Haines, Jonathan L

    2016-01-01

    Age-related macular degeneration (AMD), a highly prevalent and impactful disease of aging, is inarguably influenced by complex interactions between genetic and environmental factors. Various risk scores have been tested that assess measurable genetic and environmental contributions to disease. We herein summarize and review the ability and utility of these numerous models for prediction of AMD and suggest additional risk factors to be incorporated into clinically useful predictive models of AMD. PMID:26959068

  16. Flavonoids and Age Related Disease: Risk, benefits and critical windows

    PubMed Central

    Prasain, JK; Carlson, SH; Wyss, JM

    2010-01-01

    Plant derived products are consumed by a large percentage of the population to prevent, delay and ameliorate disease burden; however, relatively little is known about the efficacy, safety and underlying mechanisms of these traditional health products, especially when taken in concert with pharmaceutical agents. The flavonoids are a group of plant metabolites that are common in the diet and appear to provide some health benefits. While flavonoids are primarily derived from soy, many are found in fruits, nuts and more exotic sources, e.g., kudzu. Perhaps the strongest evidence for the benefits of flavonoids in diseases of aging relates to their effect on components of the metabolic syndrome. Flavonoids from soy, grape seed, kudzu and other sources all lower arterial pressure in hypertensive animal models and in a limited number of tests in humans. They also decrease the plasma concentration of lipids and buffer plasma glucose. The underlying mechanisms appear to include antioxidant actions, central nervous system effects, gut transport alterations, fatty acid sequestration and processing, PPAR activation and increases in insulin sensitivity. In animal models of disease, dietary flavonoids also demonstrate a protective effect against cognitive decline, cancer and metabolic disease. However, research also indicates that the flavonoids can be detrimental in some settings and, therefore, are not universally safe. Thus, as the population ages, it is important to determine the impact of these agents on prevention/attenuation of disease, including optimal exposure (intake, timing/duration) and potential contraindications. PMID:20181448

  17. Growth factors, aging and age-related diseases.

    PubMed

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

  18. Age-related Macular Degeneration: Genetic and Environmental Factors of Disease

    PubMed Central

    Chen, Yuhong; Bedell, Matthew; Zhang, Kang

    2010-01-01

    Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as the population ages; however, treatment options remain limited because the etiology and pathogenesis of AMD are incompletely defined. Recently, much progress has been made in gene discovery and mechanistic studies, which clearly indicate that AMD involves the interaction of multiple genetic and environmental factors. The identification of genes that have a substantial impact on the risk for AMD is not only facilitating the diagnosis and screening of populations at risk but is also elucidating key molecular pathways of pathogenesis. Pharmacogenetic studies of treatment responsiveness among patients with the “wet” form of AMD are increasingly proving to be clinically relevant; pharmacogenetic approaches hold great promise for both identifying patients with the best chance for vision recovery as well as tailoring individualized therapies. PMID:21045241

  19. Flavonoid intake and the risk of age-related cataract in China's Heilongjiang Province

    PubMed Central

    Ma, Yingna; Gao, Weiqi; Wu, Kun; Bao, Yongping

    2015-01-01

    Background/objectives Epidemiological evidence suggests that diets rich in flavonoids may reduce the risk of developing age-related cataract (ARC). Flavonoids are widely distributed in foods of plant origin, and the objective of this study was to evaluate retrospectively the association between the intakes of the five flavonoid subclasses and the risk of ARC. Subjects/methods A population-based case-control study (249 cases and 66 controls) was carried out in Heilongjiang province, which is located in the northeast of China, and where intakes and availability of fresh vegetables and fruits can be limited. Dietary data gathered by food-frequency questionnaire (FFQ) were used to calculate flavonoid intake. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression. Results No linear associations between risk of developing ARC and intakes of total dietary flavonoids, anthocyanidins, flavon-3-ol, flavanone, total flavones or total flavonols were found, but quercetin and isorhamnetin intake was inversely associated with ARC risk (OR 11.78, 95% CI: 1.62–85.84, p<0.05, and OR 6.99, 95% CI: 1.12–43.44, p<0.05, quartile 4 vs. quartile 1, respectively). Conclusion As quercetin is contained in many plant foods and isorhamnetin in very few foods, we concluded that higher quercetin intake may be an important dietary factor in the reduction of the risk of ARC. PMID:26652740

  20. Assessing Susceptibility to Age-Related Macular Degeneration With Genetic Markers and Environmental Factors

    PubMed Central

    Chen, Yuhong; Zeng, Jiexi; Zhao, Chao; Wang, Kevin; Trood, Elizabeth; Buehler, Jeanette; Weed, Matthew; Kasuga, Daniel; Bernstein, Paul S.; Hughes, Guy; Fu, Victoria; Chin, Jessica; Lee, Clara; Crocker, Maureen; Bedell, Matthew; Salasar, Francesca; Yang, Zhenglin; Goldbaum, Michael; Ferreyra, Henry; Freeman, William R.; Kozak, Igor; Zhang, Kang

    2014-01-01

    Objectives To evaluate the independent and joint effects of genetic factors and environmental variables on advanced forms of age-related macular degeneration (AMD), including geographic atrophy and choroidal neovascularization, and to develop a predictive model with genetic and environmental factors included. Methods Demographic information, including age at onset, smoking status, and body mass index, was collected for 1844 participants. Genotypes were evaluated for 8 variants in 5 genes related to AMD. Unconditional logistic regression analyses were performed to generate a risk predictive model. Results All genetic variants showed a strong association with AMD. Multivariate odds ratios were 3.52 (95% confidence interval, 2.08-5.94) for complement factor H, CFH rs1061170 CC, 4.21 (2.30-7.70) for CFH rs2274700 CC, 0.46 (0.27-0.80) for C2 rs9332739 CC/CG, 0.44 (0.30-0.66) for CFB rs641153 TT/CT, 10.99 (6.04-19.97) for HTRA1/LOC387715 rs10490924 TT, and 2.66 (1.43-4.96) for C3 rs2230199 GG. Smoking was independently associated with advanced AMD after controlling for age, sex, body mass index, and all genetic variants. Conclusion CFH confers more risk to the bilaterality of geographic atrophy, whereas HTRA1/LOC387715 contributes more to the bilaterality of choroidal neovascularization. C3 confers more risk for geographic atrophy than choroidal neovascularization. Risk models with combined genetic and environmental factors have notable discrimination power. Clinical Relevance Early detection and risk prediction of AMD could help to improve the prognosis of AMD and to reduce the outcome of blindness. Targeting high-risk individuals for surveillance and clinical interventions may help reduce disease burden. PMID:21402993

  1. Association between vitamin D status and age-related macular degeneration by genetic risk

    PubMed Central

    Millen, Amy E.; Meyers, Kristin J; Liu, Zhe; Engelman, Corinne D; Wallace, Robert B; LeBlanc, Erin S; Tinker, Lesley F.; Iyengar, Sudha K; Robinson, Jennifer; Sarto, Gloria E.; Mares, Julie A

    2016-01-01

    Importance Deficient 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with increased odds of age-related macular degeneration (AMD). Objective We examined 1) whether this association is modified by genetic risk for AMD and 2) if there is an association between AMD and single nucleotide polymorphisms (SNPs) of genes involved in vitamin D transport, metabolism and genomic function. Design, Setting and Participants Women were postmenopausal and participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS) (54 to <75 years) with available serum 25(OH)D concentrations (assessed from 1994–1998), genetic data, and measures of AMD (n=142) assessed at CAREDS baseline from 2001–2004 (n=913). Main Outcomes and Measures Prevalent early or late AMD was determined from graded, stereoscopic fundus photographs. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for AMD by the joint effects of 25(OH)D (<30, ≥30 to <50, ≥50 to <75, and ≥75 nmol/L) and risk genotype (noncarrier, one, or two risk alleles). The referent group was noncarriers with adequate vitamin D status (≥75 nmol/L). Joint effect ORs were adjusted for age, smoking, iris pigmentation, self-reported cardiovascular disease, self-reported diabetes status, and hormone use. Additive and multiplicative interactions were assessed using the Synergy Index (SI) and an interaction term, respectively. Results We observed a 6.7-fold increased odds of AMD (95% CI=1.6, 28.2) among women with deficient vitamin D status (25(OH)D<30 nmol/L) and two risk alleles for complement factor H (CFH) Y402H (SI for additive interaction=1.4, 95% CI=1.1, 1.7; p for multiplicative interaction=0.25,. A significant additive (SI=1.4, 95% CI=1.1, 1.7) and multiplicative interaction (p=0.02) was observed for deficient women with two high risk complement factor I (CFI) (rs10033900) alleles (OR=6.3, 95% CI=1.6, 24.2). The odds of AMD did not differ by genotype of candidate

  2. Age-related deficit accumulation and the risk of late-life dementia

    PubMed Central

    2014-01-01

    Introduction Many age-related health problems have been associated with dementia, leading to the hypothesis that late-life dementia may be determined less by specific risk factors, and more by the operation of multiple health deficits in the aggregate. Our study addressed (a) how the predictive value of dementia risk varies by the number of deficits considered and (b) how traditional (for example. vascular risks) and nontraditional risk factors (for example, foot problems, nasal congestion) compare in their predictive effects. Methods Older adults in the Canadian Study of Health and Aging who were cognitively healthy at baseline were analyzed (men, 2,902; women, 4,337). Over a 10-year period, 44.8% of men and 33.4% of women died; 7.4% of men and 9.1% of women without baseline cognitive impairment developed dementia. Self-rated health problems, including, but not restricted to, dementia risk factors, were coded as deficit present/absent. Different numbers of randomly selected variables were used to calculate various iterations of the index (that is, the proportion of deficits present in an individual. Risks for 10-year mortality and dementia outcomes were evaluated separately for men and women by using logistic regression, adjusted for age. The prediction accuracy was evaluated by using C-statistics. Results Age-adjusted odds ratios per additional deficit were 1.22 (95% confidence interval (CI), 1.18 to 1.26) in men and 1.14 (1.11 to 1.16) in women in relation to death, and 1.18 (1.12 to 1.25) in men and 1.08 (1.04 to 1.11) in women in relation to dementia. The predictive value increased with the number (n) of deficits considered, regardless of whether they were known dementia risks, and stabilized at n > 25. The all-factor index best predicted dementia (C-statistics, 0.67 ± 0.03). Conclusions The variety of items associated with dementias suggests that some part of the risk might relate more to aberrant repair processes, than to specifically toxic results

  3. Rare Complement Factor H Variant Associated With Age-Related Macular Degeneration in the Amish

    PubMed Central

    Hoffman, Joshua D.; CookeBailey, Jessica N.; D'Aoust, Laura; Cade, William; Ayala-Haedo, Juan; Fuzzell, Denise; Laux, Renee; Adams, Larry D.; Reinhart-Mercer, Lori; Caywood, Laura; Whitehead-Gay, Patrice; Agarwal, Anita; Wang, Gaofeng; Scott, William K.; Pericak-Vance, Margaret A.; Haines, Jonathan L.

    2014-01-01

    Purpose. Age-related macular degeneration is the leading cause of blindness among the adult population in the developed world. To further the understanding of this disease, we have studied the genetically isolated Amish population of Ohio and Indiana. Methods. Cumulative genetic risk scores were calculated using the 19 known allelic associations. Exome sequencing was performed in three members of a small Amish family with AMD who lacked the common risk alleles in complement factor H (CFH) and ARMS2/HTRA1. Follow-up genotyping and association analysis was performed in a cohort of 973 Amish individuals, including 95 with self-reported AMD. Results. The cumulative genetic risk score analysis generated a mean genetic risk score of 1.12 (95% confidence interval [CI]: 1.10, 1.13) in the Amish controls and 1.18 (95% CI: 1.13, 1.22) in the Amish cases. This mean difference in genetic risk scores is statistically significant (P = 0.0042). Exome sequencing identified a rare variant (P503A) in CFH. Association analysis in the remainder of the Amish sample revealed that the P503A variant is significantly associated with AMD (P = 9.27 × 10−13). Variant P503A was absent when evaluated in a cohort of 791 elderly non-Amish controls, and 1456 non-Amish cases. Conclusions. Data from the cumulative genetic risk score analysis suggests that the variants reported by the AMDGene consortium account for a smaller genetic burden of disease in the Amish compared with the non-Amish Caucasian population. Using exome sequencing data, we identified a novel missense mutation that is shared among a densely affected nuclear Amish family and located in a gene that has been previously implicated in AMD risk. PMID:24906858

  4. Genetic factors associated with the development of age-related macular degeneration.

    PubMed

    Sergejeva, Olga; Botov, Roman; Liutkevičienė, Rasa; Kriaučiūnienė, Loresa

    2016-01-01

    Age-related macular degeneration (AMD) affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people aged more than 60 years. This disease affects 2.5 million individuals in Europe. AMD is caused by both environmental and genetic factors. Numerous risk factors have been reported, but the pathogenesis of AMD is complex and fairly understood. Age, female gender, obesity, race, education status, family history, hyperopia, iris color, cigarette smoking, previous cataract surgery, history of cardiovascular and cerebrovascular disease, diabetes, sunlight exposure and many other factors have been shown to be associated with AMD development. Scientific evidence shows that genes may play a role in the development of nearly 3 out of 4 cases of this devastating eye disease. The genes that have been shown to be associated with AMD are genes encoding complement system components such as CFH, C2, C3, CFB, and other. PMID:27170480

  5. Complement factor H gene polymorphisms and Chlamydia pneumoniae infection in age-related macular degeneration

    PubMed Central

    Haas, P; Steindl, K; Schmid-Kubista, KE; Aggermann, T; Krugluger, W; Hageman, GS; Binder, S

    2014-01-01

    Purpose To investigate the association of the complement factor H gene (CFH) Y402H polymorphism and age-related macular degeneration (AMD) in the Austrian population (Caucasoid descent), and to determine whether there is an association between exposure to Chlamydia pneumoniae—responsible for up to 20% of community-acquired pneumoniae—and the AMD-associated CFH risk polymorphism. Methods Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 75 unrelated AMD patients and compared with 75 healthy, age-matched control subjects. C. pneumoniae serum IgG was tested by ELISA (R&D) in both groups. The association between the CFH Y402H genetic polymorphism and the disease was examined by χ2-test and logistic regression. Results CFH Y402H genotype frequencies differed significantly between AMD patients and healthy controls (1277 TT, 22.7%; 1277 TC, 53.3%; and 1277 CC, 22.7% in the AMD group; 1277 TT, 48.0%; 1277 TC, 38.7%; and 1277 CC, 13.3% in the control group) showing a P-value <0.005 (OR:2.920/3.811). No association was found between a positive C. pneumoniae titre and AMD (P = 0.192), nor was any association found between C. pneumoniae and the CFH Y402H polymorphism. Conclusions Our data confirm that the CFH Y402H polymorphism is a risk factor for AMD in the Austrian population with a higher frequency of the Y402 polymorphism in AMD patients. No association between preceding C. pneumoniae infection and diagnosed AMD was found. PMID:19169230

  6. Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

    PubMed

    Ishii, Makoto; Iadecola, Costantino

    2016-05-01

    Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26546479

  7. Younger siblings, C-reactive protein, and risk of age-related macular degeneration.

    PubMed

    Cohn, Amy C; Busija, Lucy; Robman, Liubov D; Dimitrov, Peter N; Varsamidis, Mary; Lim, Lyndell L; Baird, Paul N; Guymer, Robyn H

    2013-05-01

    In this study, we examined the relationship between exposure to siblings and 1) the risk of age-related macular degeneration (AMD) and 2) C-reactive protein levels. We retrospectively analyzed pooled cross-sectional data from 2 studies: the Cardiovascular Health and Age-Related Maculopathy Study (2001-2002) and the Age-Related Maculopathy Statin Study (2004-2006). Associations between number of siblings and AMD were assessed by using multinomial logistic regression. Associations between number of siblings and C-reactive protein levels were examined by using a generalized linear model for γ distribution. A higher number of younger siblings was associated with significantly lower odds of early AMD in those with a family history of AMD (odds ratio = 0.2, 95% confidence interval: 0.1, 0.8) (P = 0.022) but was unrelated to AMD for those who had no family history of the disease (odds ratio = 1.0, 95% confidence interval: 0.9, 1.2) (P = 0.874). A higher number of younger siblings correlated with lower C-reactive protein levels (β = -0.19, 95% confidence interval: -0.38, -0.01) (P = 0.036). This supports the theory that immune modulation contributes to AMD pathogenesis and suggests that exposure to younger siblings might be protective when there is a family history of AMD. PMID:23548752

  8. Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume.

    PubMed

    Erickson, Kirk I; Prakash, Ruchika Shaurya; Voss, Michelle W; Chaddock, Laura; Heo, Susie; McLaren, Molly; Pence, Brandt D; Martin, Stephen A; Vieira, Victoria J; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2010-04-14

    Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood. PMID:20392958

  9. Genome-wide association analyses of genetic, phenotypic, and environmental risks in the age-related eye disease study

    PubMed Central

    Ryu, Euijung; Fridley, Brooke L.; Tosakulwong, Nirubol; Bailey, Kent R.

    2010-01-01

    Purpose To present genome-wide association analyses of genotypic and environmental risks on age-related macular degeneration (AMD) using 593 subjects from the age-related eye disease study (AREDS), after adjusting for population stratification and including questionable controls. Methods Single nucleotide polymorphism (SNP) associations with AMD for the non-Hispanic white population were investigated using a log-additive model after adjusting for population stratification. Replication of possible SNP-disease association was performed by genotyping an independent group of 444 AMD case and 300 control subjects. Logistic regression models were used to assess interaction effects between smoking and SNPs associated with AMD. Independent genetic risk effects among the disease-associated SNPs were also investigated using multiple logistic regression models. Results Population stratification was observed among the individuals having a self-reported race of non-Hispanic white. Risk allele frequencies at established AMD loci demonstrated that questionable control subjects were similar to control subjects in the AREDS, suggesting that they could be used as true controls in the analyses. Genetic loci (complement factor H [CFH], complement factor B [CFB], the age-related maculopathy susceptibility 2 locus containing the hypothetical gene [LOC387715]/the high-temperature requirement A-1 [HTRA1], and complement component 3 [C3]) that were already known to be associated with AMD were identified. An additional 26 novel SNPs potentially associated with AMD were identified, but none were definitely replicated in a second independent group of subjects. Smoking did not interact with known AMD loci, but was associated with late AMD. Statistically independent genetic signals were observed within the Pleckstrin homology domain-containing family A member 1 (PLEKHA1) region near LOC387715/HTRA1 and within a haplotype spanning exon 19 of the C3 gene. Conclusions Population stratification

  10. A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

  11. Age-related changes of mitochondrial transcription factor a expression in rotator cuff degeneration

    PubMed Central

    Ichiseki, Toru; Ueda, Shusuke; Ueda, Yoshimichi; Kaneuji, Ayumi; Kawahara, Norio; Matsumoto, Tadami

    2015-01-01

    One cause of rotator cuff tears is thought to be age-related degenerative changes occurring in the rotator cuff. Using Rat rotator cuff we determined age-related changes in mitochondrial transcription factor A (TFAM) expression in rotator cuff degeneration to clarify the presence/absence of mitochondrial stress. The materials used were rotator cuffs (supraspinatus) of 5-, 24-, 48-, and 100-week-old Wistar Rats (five animals each). Histopathological study revealed a 4-layer structure consisting of a bone layer, calcified cartilage layer, non-calcified cartilage layer, and tendinous component), with age-related narrowing of the non-calcified cartilage layer confirmed to be present. In an immunohistochemical TFAM study positive findings of the non-calcified cartilage layer were less prominent in the 100-week-old group. In an Enzyme-Linked Immunosorbent Assay (ELISA) study, these were more prominent in the 5-week-old to 24-week-old groups, and slightly less so in the 48-week-old group as compared to the 24-week-old one. In the 100-week-old group as compared to the 24-week-old one they were significantly less prominent (p<0.05). The non-calcified cartilage layer is a major site for the dispersion of mechanical energy, and the change in TFAM expression noted at the same site in the present study and the results of ELISA suggest that age-related changes in mitochondrial stress may be one cause of rotator cuff degeneration. PMID:26692954

  12. Quantifying risk over the life course - latency, age-related susceptibility, and other time-varying exposure metrics.

    PubMed

    Wang, Molin; Liao, Xiaomei; Laden, Francine; Spiegelman, Donna

    2016-06-15

    Identification of the latency period and age-related susceptibility, if any, is an important aspect of assessing risks of environmental, nutritional, and occupational exposures. We consider estimation and inference for latency and age-related susceptibility in relative risk and excess risk models. We focus on likelihood-based methods for point and interval estimation of the latency period and age-related windows of susceptibility coupled with several commonly considered exposure metrics. The method is illustrated in a study of the timing of the effects of constituents of air pollution on mortality in the Nurses' Health Study. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26750582

  13. Risk Characteristics of the Combined Geographic Atrophy and Choroidal Neovascularisation Phenotype in Age-Related Macular Degeneration

    PubMed Central

    Saade, Celine; Ganti, Bhaskar; Marmor, Michael; Freund, K. Bailey; Smith, R. Theodore

    2014-01-01

    Aim To investigate the risk characteristics of the combined geographic atrophy (GA) and choroidal neovascularization (CNV) phenotype of age-related macular degeneration (AMD) compared to GA or CNV. Methods Patients with advanced AMD were identified and divided into three groups using multimodal imaging: patients with GA in at least one eye, patients with CNV in at least one eye, and patients with simultaneous GA and CNV in at least one eye. Epidemiologic and clinical factors were gathered from patient questionnaires. Genotypes for age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) were determined. Results 42 patients with GA or CNV and 16 patients with combined GA/CNV were identified. Patients with the combined phenotype were older (86.4 vs. 81.8 years, p=0.049) and had a higher prevalence of advanced AMD in the fellow eye (81.3% vs. 31.0%, p<0.001). CFH and ARMS2 risk alleles were not associated with the combined phenotype. Conclusion The combined GA/CNV phenotype has similar epidemiologic, clinical, and genetic features as GA and CNV but occurs at an older age and is more associated with advanced AMD in the fellow eye, suggesting that all these phenotypes are part of the same spectrum of disease and that the combined phenotype represents an even more advanced form of AMD than either GA or CNV. PMID:25091949

  14. Young systemic factors as a medicine for age-related neurodegenerative diseases

    PubMed Central

    Katsimpardi, Lida; Rubin, Lee L

    2015-01-01

    It is widely known that neurogenesis, brain function and cognition decline with aging. Increasing evidence suggests that cerebrovascular dysfunction is a major cause of cognitive impairment in the elderly but is also involved in age-related neurodegenerative diseases. Finding ways and molecules that reverse this process and ameliorate age- and disease-related cognitive impairment by targeting vascular and neurogenic deterioration would be of great therapeutic value. In Katsimpardi et al. we reported that young blood has a dual beneficial effect in the aged brain by restoring age-related decline in neurogenesis as well as inducing a striking remodeling of the aged vasculature and restoring blood flow to youthful levels. Additionally, we identified a youthful systemic factor, GDF11 that recapitulates these beneficial effects of young blood. We believe that the identification of young systemic factors that can rejuvenate the aged brain opens new roads to therapeutic intervention for neurodegenerative diseases by targeting both neural stem cells and neurogenesis as well as at the vasculature.

  15. Age-related differences in emotion regulation strategies: Examining the role of contextual factors.

    PubMed

    Schirda, Brittney; Valentine, Thomas R; Aldao, Amelia; Prakash, Ruchika Shaurya

    2016-09-01

    Increasing age is characterized by greater positive affective states. However, there is mixed evidence on the implementation of emotion regulation strategies across the life span. To clarify the discrepancies in the literature, we examined the modulating influence of contextual factors in understanding emotion regulation strategy use in older and young adults. Forty-eight older adults and forty-nine young adults completed a retrospective survey inquiring about the use of emotion regulation strategies in emotion-eliciting situations experienced over the preceding 2 weeks. We used factor analysis to establish clusters of emotion regulation strategies, resulting in cognitive strategies, acceptance, and maladaptive strategies. Overall, we found context-dependent age-related differences in emotion regulation strategy use. Specifically, older adults reported greater use of acceptance than young adults in situations of moderate intensity and in situations that evoke anxiety and sadness. In addition, older adults reported using maladaptive strategies to a lesser extent in high- and moderate-intensity situations and in situations that elicit anxiety and sadness when compared with young adults. There were no age-related differences in the use of cognitive strategies across contexts. Older adults, compared to young adults, reported less use of maladaptive strategies and greater use of acceptance than young adults, which suggests that the enhanced emotional functioning observed later in life may be due to a shift in strategy implementation. (PsycINFO Database Record PMID:27570980

  16. Morbidity risks among older adults with pre-existing age-related diseases.

    PubMed

    Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Kulminski, Alexander; Yashin, Anatoliy I

    2013-12-01

    Multi-morbidity is common among older adults; however, for many aging-related diseases there is no information for U.S. elderly population on how earlier-manifested disease affects the risk of another disease manifested later during patient's lifetime. Quantitative evaluation of risks of cancer and non-cancer diseases for older adults with pre-existing conditions is performed using the Surveillance, Epidemiology, and End Results (SEER) Registry data linked to the Medicare Files of Service Use (MFSU). Using the SEER-Medicare data containing individual records for 2,154,598 individuals, we empirically evaluated age patterns of incidence of age-associated diseases diagnosed after the onset of earlier manifested disease and compared these patterns with those in general population. Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services/procedures, and Medicare enrollment/disenrollment. More than threefold increase of subsequent diseases risk was observed for 15 disease pairs, majority of them were i) diseases of the same organ and/or system (e.g., Parkinson disease for patients with Alzheimer disease, HR=3.77, kidney cancer for patients with renal failure, HR=3.28) or ii) disease pairs with primary diseases being fast-progressive cancers (i.e., lung, kidney, and pancreas), e.g., ulcer (HR=4.68) and melanoma (HR=4.15) for patients with pancreatic cancer. Lower risk of subsequent disease was registered for 20 disease pairs, mostly among patients with Alzheimer's or Parkinson's disease, e.g., decreased lung cancer risk among patients with Alzheimer's (HR=0.64) and Parkinson's (HR=0.60) disease. Synergistic and antagonistic dependences in geriatric disease risks were observed among US elderly confirming known and detecting new associations of wide spectrum of age-associated diseases. The results can be used in optimization of screening, prevention and treatment strategies of chronic diseases among U.S. elderly

  17. The association between statin use and risk of age-related macular degeneration

    PubMed Central

    Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

    2015-01-01

    The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

  18. Analysis of Risk Alleles and Complement Activation Levels in Familial and Non-Familial Age-Related Macular Degeneration

    PubMed Central

    Saksens, Nicole T. M.; Lechanteur, Yara T. E.; Verbakel, Sanne K.; Groenewoud, Joannes M. M.; Daha, Mohamed R.; Schick, Tina; Fauser, Sascha; Boon, Camiel J. F.; Hoyng, Carel B.; den Hollander, Anneke I.

    2016-01-01

    Aims Age-related macular degeneration (AMD) is a multifactorial disease, in which complement-mediated inflammation plays a pivotal role. A positive family history is an important risk factor for developing AMD. Certain lifestyle factors are shown to be significantly associated with AMD in non-familial cases, but not in familial cases. This study aimed to investigate whether the contribution of common genetic variants and complement activation levels differs between familial and sporadic cases with AMD. Methods and Results 1216 AMD patients (281 familial and 935 sporadic) and 1043 controls (143 unaffected members with a family history of AMD and 900 unrelated controls without a family history of AMD) were included in this study. Ophthalmic examinations were performed, and lifestyle and family history were documented with a questionnaire. Nine single nucleotide polymorphisms (SNPs) known to be associated with AMD were genotyped, and serum concentrations of complement components C3 and C3d were measured. Associations were assessed in familial and sporadic individuals. The association with risk alleles of the age-related maculopathy susceptibility 2 (ARMS2) gene was significantly stronger in sporadic AMD patients compared to familial cases (p = 0.017 for all AMD stages and p = 0.003 for advanced AMD, respectively). ARMS2 risk alleles had the largest effect in sporadic cases but were not significantly associated with AMD in densely affected families. The C3d/C3 ratio was a significant risk factor for AMD in sporadic cases and may also be associated with familial cases. In patients with a densely affected family this effect was particularly strong with ORs of 5.37 and 4.99 for all AMD and advanced AMD respectively. Conclusion This study suggests that in familial AMD patients, the common genetic risk variant in ARMS2 is less important compared to sporadic AMD. In contrast, factors leading to increased complement activation appear to play a larger role in patients with a

  19. Role of macrophage migration inhibitory factor in age-related lung disease.

    PubMed

    Sauler, Maor; Bucala, Richard; Lee, Patty J

    2015-07-01

    The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

  20. Susceptibility to advanced age-related macular degeneration and alleles of complement factor H, complement factor B, complement component 2, complement component 3, and age-related maculopathy susceptibility 2 genes in a Mexican population

    PubMed Central

    Buentello-Volante, Beatriz; Rodriguez-Ruiz, Gabriela; Miranda-Duarte, Antonio; Pompa-Mera, Ericka N.; Graue-Wiechers, Federico; Bekker-Méndez, Carolina; Ayala-Ramirez, Raul; Quezada, Carlos; Rodríguez-Loaiza, Jose L.

    2012-01-01

    Purpose To investigate the association of age-related macular degeneration (AMD)–high risk alleles of the complement factor H (CFH), complement factor B (CFB), complement component 2 (C2), complement component 3 (C3), and age-related maculopathy susceptibility 2 (ARMS2) genes in a Mexican population for the first time. Methods Genotyping was performed for the Y402H variant of CFH, for the L9H, R32Q, and K565E variants of CFB, the E318D variant of C2, the A69S variant of ARMS2, and the R102G variant of C3 in 159 Mexican mestizo patients at advanced stages of AMD, i.e., CARMS (Clinical Age-Related Maculopathy Staging System) grade 4 or 5. The frequency of these variants was also investigated in a group of 152 control subjects without AMD. Genomic DNA was extracted from blood leukocytes, and genotyping was performed using PCR followed by direct sequencing. Allele-specific restriction enzyme digestion was used to detect the R102G polymorphism in C3. Results There were significant differences in the allelic distribution between the two groups for CFH Y402H (p=1×10−5), ARMS A69S (p=4×10−7), and CFB R32Q (p=0.01). The odds ratios (95% confidence interval) obtained for the risk alleles of these three variants were 3.8 (2.4–5.9), 3.04 (2.2–4.3), and 2.5 (1.1–5.7), respectively. Haplotype analysis including the two most significantly associated alleles (CFH Y402H and ARMS A69S) indicated that the C-T combination conferred an odds ratio (95% confidence interval) of 6.9 (3.2–14.8). The exposed attributable risk for this particular haplotype was 85.5%. Conclusions This is the first case-control investigation of AMD–high risk alleles in a Latino population. Our results support that CFH, ARMS2, and CFB AMD-risk alleles are consistently associated with the disease, even in ethnic groups with a complex admixture of ancestral populations such as Mexican mestizos. PMID:23112567

  1. Insulin-like growth factor 2 rescues aging-related memory loss in rats.

    PubMed

    Steinmetz, Adam B; Johnson, Sarah A; Iannitelli, Dylan E; Pollonini, Gabriella; Alberini, Cristina M

    2016-08-01

    Aging is accompanied by declines in memory performance, and particularly affects memories that rely on hippocampal-cortical systems, such as episodic and explicit. With aged populations significantly increasing, the need for preventing or rescuing memory deficits is pressing. However, effective treatments are lacking. Here, we show that the level of the mature form of insulin-like growth factor 2 (IGF-2), a peptide regulated in the hippocampus by learning, required for memory consolidation and a promoter of memory enhancement in young adult rodents, is significantly reduced in hippocampal synapses of aged rats. By contrast, the hippocampal level of the immature form proIGF-2 is increased, suggesting an aging-related deficit in IGF-2 processing. In agreement, aged compared to young adult rats are deficient in the activity of proprotein convertase 2, an enzyme that likely mediates IGF-2 posttranslational processing. Hippocampal administration of the recombinant, mature form of IGF-2 rescues hippocampal-dependent memory deficits and working memory impairment in aged rats. Thus, IGF-2 may represent a novel therapeutic avenue for preventing or reversing aging-related cognitive impairments. PMID:27318130

  2. Age-Related Changes in Immunological Factors and Their Relevance in Allergic Disease Development During Childhood

    PubMed Central

    Chang, Woo-Sung; Kim, Eun-Jin; Lim, Yeon-Mi; Yoon, Dankyu; Son, Jo-Young; Park, Jung-Won; Hong, Soo-Jong; Cho, Sang-Heon

    2016-01-01

    Purpose Allergic diseases are triggered by Th2-mediated immune reactions to allergens and orchestrated by various immunological factors, including immune cells and cytokines. Although many reports have suggested that childhood is the critical period in the onset of allergic diseases and aging leads to alter the susceptibility of an individual to allergic diseases, age-related changes in various immunological factors in healthy individuals as well as their difference between healthy and allergic children have not yet been established. Methods We investigated the ratio of Th1/Th2 cells and the levels of 22 allergy-related cytokines across all age groups in individuals who were classified as clinically non-atopic and healthy. We also examined their differences between healthy and allergic children to evaluate immunological changes induced by the development of allergic diseases during childhood. Results The Th1/Th2 ratio rose gradually during the growth period including childhood, reaching peak values in the twenties-thirties age group. Th1/Th2 ratios were significantly lower in allergic children than in healthy controls, whereas 14 of 22 cytokines were significantly higher in allergic children than in healthy controls. On the other hand, there were no differences in Th1/Th2 ratios and cytokines between healthy and allergic adolescents. Conclusions In this study, age-related changes in Th1/Th2 ratios were found in normal controls across all age groups, and decreases in Th1/Th2 ratio were observed with increasing of 14 cytokines in allergic children. The results of this study may be helpful as reference values for both monitoring immunological changes according to aging in healthy individuals and distinguishing between normal and allergic subjects in terms of immune cells and soluble factors. PMID:27126727

  3. Natural history of age-related lobular involution and impact on breast cancer risk.

    PubMed

    Radisky, Derek C; Visscher, Daniel W; Frank, Ryan D; Vierkant, Robert A; Winham, Stacey; Stallings-Mann, Melody; Hoskin, Tanya L; Nassar, Aziza; Vachon, Celine M; Denison, Lori A; Hartmann, Lynn C; Frost, Marlene H; Degnim, Amy C

    2016-02-01

    Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk. PMID:26846985

  4. Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

  5. Prospective Study of Plasma Homocysteine Level and Risk of Age-related Macular Degeneration in Women

    PubMed Central

    Christen, William G.; Cook, Nancy R.; Ridker, Paul M.; Buring, Julie E.

    2014-01-01

    Purpose Prospective data to examine the association of homocysteine and age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. Methods We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results During an average of 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually-significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.95–1.63; p for trend, 0.07) and visually-significant AMD (HR, 1.41; 95% CI, 0.92–2.17; p for trend, 0.052) in age- and treatment-adjusted analyses. Conclusions These prospective data from a large cohort of apparently-healthy women do not support a strong role for homocysteine in AMD occurrence. PMID:25777307

  6. Search for age-related macular degeneration risk variants in Alzheimer disease genes and pathways.

    PubMed

    Logue, Mark W; Schu, Matthew; Vardarajan, Badri N; Farrell, John; Lunetta, Kathryn L; Jun, Gyungah; Baldwin, Clinton T; Deangelis, Margaret M; Farrer, Lindsay A

    2014-06-01

    Several lines of inquiry point to overlapping molecular mechanisms between late-onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We evaluated summarized results from large genome-wide association studies for AD and AMD to test the hypothesis that AD susceptibility loci are also associated with AMD. We observed association of both disorders with genes in a region of chromosome 7, including PILRA and ZCWPW1 (peak AMD SNP rs7792525, minor allele frequency [MAF] = 19%, odds ratio [OR] = 1.14, p = 2.34 × 10(-6)), and with ABCA7 (peak AMD SNP rs3752228, MAF = 0.054, OR = 1.22, p = 0.00012). Next, we evaluated association of AMD with genes in AD-related pathways identified by canonical pathway analysis of AD-associated genes. Significant associations were observed with multiple previously identified AMD risk loci and 2 novel genes: HGS (peak SNP rs8070488, MAF = 0.23, OR = 0.91, p = 7.52 × 10(-5)), which plays a role in the clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590, MAF = 0.34, OR = 0.89, p = 1.17 × 10(-5)), which is a member of the atherosclerosis signaling and the LXR/RXR activation pathways. Our results suggest that AMD and AD share genetic mechanisms. PMID:24439028

  7. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration

    PubMed Central

    Solomon, Sharon D.; Lindsley, Kristina; Vedula, Satyanarayana S.; Krzystolik, Magdalena G.; Hawkins, Barbara S.

    2014-01-01

    Background Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. Objectives To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. Selection criteria We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Data collection

  8. Antivascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

    PubMed Central

    Zampros, Ilias; Praidou, Anna; Brazitikos, Periklis; Ekonomidis, Panagiotis; Androudi, Sofia

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF) is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV), which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA) are also discussed for their promising outcomes. PMID:22174998

  9. MITOCHONDRIAL VARIATION AND THE RISK OF AGE-RELATED MACULAR DEGENERATION ACROSS DIVERSE POPULATIONS

    PubMed Central

    RESTREPO, NICOLE A.; MITCHELL, SABRINA L.; GOODLOE, ROBERT J.; MURDOCK, DEBORAH G.; HAINES, JONANTHAN L.; CRAWFORD, DANA C.

    2014-01-01

    Substantial progress has been made in identifying susceptibility variants for age-related macular degeneration (AMD). The majority of research to identify genetic variants associated with AMD has focused on nuclear genetic variation. While there is some evidence that mitochondrial genetic variation contributes to AMD susceptibility, to date, these studies have been limited to populations of European descent resulting in a lack of data in diverse populations. A major goal of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study is to describe the underlying genetic architecture of common, complex diseases across diverse populations. This present study sought to determine if mitochondrial genetic variation influences risk of AMD across diverse populations. We performed a genetic association study to investigate the contribution of mitochondrial DNA variation to AMD risk. We accessed samples from the National Health and Nutrition Examination Surveys, a U.S population-based, cross-sectional survey collected without regard to health status. AMD cases and controls were selected from the Third NHANES and NHANES 2007-2008 datasets which include non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. AMD cases were defined as those > 60 years of age with early/late AMD, as determined by fundus photography. Targeted genotyping was performed for 63 mitochondrial SNPs and participants were then classified into mitochondrial haplogroups. We used logistic regression assuming a dominant genetic model adjusting for age, sex, body mass index, and smoking status (ever vs. never). Regressions and meta-analyses were performed for individual SNPs and mitochondrial haplogroups J, T, and U. We identified five SNPs associated with AMD in Mexican Americans at p < 0.05, including three located in the control region (mt16111, mt16362, and mt16319), one in MT-RNR2 (mt1736), and one in MT-ND4 (mt12007). No mitochondrial variant or haplogroup was significantly

  10. AGE-RELATED FACTORS AFFECTING THE POST-YIELD ENERGY DISSIPATION OF HUMAN CORTICAL BONE

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Tyler, Jerrod H.; Acuna, Rae L.; Gayle, Heather J.; Wang, Xiaodu

    2007-01-01

    The risk of bone fracture depends in part on the quality of the tissue, not just the size and mass. This study assessed the post-yield energy dissipation of cortical bone in tension as a function of age and composition. Tensile specimens were prepared from tibiae of human cadavers in which male and female donors were divided into two age groups: middle aged (51 to 56 years old, n = 9) and elderly (72 to 90 years old, n = 8). By loading, unloading, and reloading a specimen with rest period inserted in between, tensile properties at incremental strain levels were assessed. In addition, the post-yield toughness was estimated and partitioned as follows: plastic strain energy related to permanent deformation, released elastic strain energy related to stiffness loss, and hysteresis energy related to viscous behavior. Porosity, mineral and collagen content, and collagen crosslinks of each specimen were also measured to determine the micro and ultrastructural properties of the tissue. It was found that age affected all the energy terms plus strength but not elastic stiffness. The post-yield energy terms were correlated with porosity, pentosidine (a marker of non-enzymatic crosslinks), and collagen content, all of which significantly varied with age. General linear models with the highest possible R2 value suggested that the pentosidine concentration and collagen content provided the best explanation of the age-related decrease in the post-yield energy dissipation of bone. Among them, pentosidine concentration had the greatest contribution to plastic strain energy and was the best explanatory variable of damage accumulation. PMID:17266142

  11. Identifying subtypes of patients with neovascular age-related macular degeneration by genotypic and cardiovascular risk characteristics

    PubMed Central

    2011-01-01

    Background One of the challenges in the interpretation of studies showing associations between environmental and genotypic data with disease outcomes such as neovascular age-related macular degeneration (AMD) is understanding the phenotypic heterogeneity within a patient population with regard to any risk factor associated with the condition. This is critical when considering the potential therapeutic response of patients to any drug developed to treat the condition. In the present study, we identify patient subtypes or clusters which could represent several different targets for treatment development, based on genetic pathways in AMD and cardiovascular pathology. Methods We identified a sample of patients with neovascular AMD, that in previous studies had been shown to be at elevated risk for the disease through environmental factors such as cigarette smoking and genetic variants including the complement factor H gene (CFH) on chromosome 1q25 and variants in the ARMS2/HtrA serine peptidase 1 (HTRA1) gene(s) on chromosome 10q26. We conducted a multivariate segmentation analysis of 253 of these patients utilizing available epidemiologic and genetic data. Results In a multivariate model, cigarette smoking failed to differentiate subtypes of patients. However, four meaningfully distinct clusters of patients were identified that were most strongly differentiated by their cardiovascular health status (histories of hypercholesterolemia and hypertension), and the alleles of ARMS2/HTRA1 rs1049331. Conclusions These results have significant personalized medicine implications for drug developers attempting to determine the effective size of the treatable neovascular AMD population. Patient subtypes or clusters may represent different targets for therapeutic development based on genetic pathways in AMD and cardiovascular pathology, and treatments developed that may elevate CV risk, may be ill advised for certain of the clusters identified. PMID:21682878

  12. Diminishing risk for age related macular degeneration with nutrition: A current view

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies because they are more affordable...

  13. Current status of vascular endothelial growth factor inhibition in age-related macular degeneration.

    PubMed

    Mousa, Shaker A; Mousa, Shaymaa S

    2010-06-01

    Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized. PMID:20210371

  14. Regulation of age-related macular degeneration-like pathology by complement factor H

    PubMed Central

    Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/− and Cfh−/− mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/− and Cfh−/− mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/− mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/− mice versus complement deficiency in Cfh−/− animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

  15. Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

    PubMed Central

    Örnek, Nurgül; Örnek, Kemal; Aydin, Süleyman; Yilmaz, Musa; Ölmez, Yaşar

    2016-01-01

    AIM To investigate the serum levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and adropin in age-related macular degeneration (AMD) patients. METHODS Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group. Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups. RESULTS AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness (P =0.01, 0.047, 0.025 and <0.001, respectively). Serum VEGFR-2 level revealed a significant decrease in AMD patients compared to controls (26.48±6.44 vs 30.42±7.92 ng/mL, P<0.001). There was an insignificant increase in serum adropin level in AMD patients (6.17±3.19 vs 5.79±2.71 ng/mL, P=0.4). Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness (r=-0.226, P=0.025) and a significant positive correlation with subfoveal choroidal thickness (r=0.2, P=0.048). CONCLUSION The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD. PMID:27162728

  16. Complement factor B polymorphism (rs641153) and susceptibility to age-related macular degeneration: evidence from published studies

    PubMed Central

    Wang, Xin; Zhang, Ying; Zhang, Mao-Nian

    2013-01-01

    AIM To determine whether single nucleotide polymorphism (SNP) rs641153 is associated with the risk of age-related macular degeneration (AMD), we performed a systematic meta-analysis of 15 eligible studies. SNP in the complement factor B (CFB) gene is considered to have significant association with AMD susceptibility, but there is great discrepancy in these results. METHODS The eligible studies were identified by searching the databases of PubMed, EMBASE, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association. All data were analyzed using Stata software. RESULTS The association between rs641153 and AMD risk was statistically significant under the homozygous model (AA vs GG:OR=0.26, 95%CI=0.15-0.45, Ph=0.973, I2=0.0%, fixed effects), dominant model (AA+GA vs GG:OR=0.49, 95%CI=0.40-0.59, Ph=0.004, I2=56.4%, random effects) and recessive model (AA vs GA+GG:OR=0.30, 95%CI=0.17-0.51, Ph=0.983, I2=0.0%, fixed effects). The same results were also observed in the stratified analyses by ethnicity, source of control and sample size. CONCLUSION Our meta-analysis suggests that rs641153 in the CFB gene may play a protective role in AMD susceptibility, the late AMD in particular, both in Caucasians and in Asians. PMID:24392338

  17. Diabetes Mellitus and Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Xue; Rong, Shi Song; Xu, Qihua; Tang, Fang Yao; Liu, Yuan; Gu, Hong; Tam, Pancy O. S.; Chen, Li Jia; Brelén, Mårten E.; Pang, Chi Pui; Zhao, Chen

    2014-01-01

    Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association. PMID:25238063

  18. Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype

    PubMed Central

    Sofat, Reecha; Casas, Juan P; Webster, Andrew R; Bird, Alan C; Mann, Samantha S; Yates, John RW; Moore, Anthony T; Sepp, Tiina; Cipriani, Valentina; Bunce, Catey; Khan, Jane C; Shahid, Humma; Swaroop, Anand; Abecasis, Gonçalo; Branham, Kari E H; Zareparsi, Sepideh; Bergen, Arthur A; Klaver, Caroline CW; Baas, Dominique C; Zhang, Kang; Chen, Yuhong; Gibbs, Daniel; Weber, Bernhard H F; Keilhauer, Claudia N; Fritsche, Lars G; Lotery, Andrew; Cree, Angela J; Griffiths, Helen L; Bhattacharya, Shomi S; Chen, Li L; Jenkins, Sharon A; Peto, Tunde; Lathrop, Mark; Leveillard, Thierry; Gorin, Michael B; Weeks, Daniel E; Ortube, Maria Carolina; Ferrell, Robert E; Jakobsdottir, Johanna; Conley, Yvette P; Rahu, Mati; Seland, Johan H; Soubrane, Gisele; Topouzis, Fotis; Vioque, Jesus; Tomazzoli, Laura; Young, Ian; Whittaker, John; Chakravarthy, Usha; de Jong, Paulus T V M; Smeeth, Liam; Fletcher, Astrid; Hingorani, Aroon D

    2012-01-01

    Background Variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case–control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking. Methods To precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, ‘Y402H’) with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26 494 individuals, including 14 174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene–smoking interaction; and 16 published studies from non-European ancestry. Results In individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10–2.45; P = 1.1 x 10−161]. There was no evidence of effect modification by smoking (P = 0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies. Conclusion The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association. PMID:22253316

  19. Neighborhood Deprivation and Risk of Age-Related Eye Diseases: A Follow-up Study in Sweden

    PubMed Central

    Hamano, Tsuyoshi; Li, Xinjun; Tanito, Masaki; Nabika, Toru; Shiwaku, Kuninori; Sundquist, Jan; Sundquist, Kristina

    2016-01-01

    Purpose To examine whether there is an association between neighborhood deprivation and age-related eye diseases, particularly macular degeneration, cataract, diabetes-related eye complications, and glaucoma. Methods The study population comprised a nationwide sample of 2,060,887 men and 2,250,851 women aged 40 years or older living in Sweden who were followed from 1 January 2000 until the first hospitalization/outpatient registration for age-related eye disease during the study period, death, emigration, or the end of the study period on 31 December 2010. Multilevel logistic regression was used to estimate the association between neighborhood deprivation and age-related eye diseases. Results In men, the odds ratio (OR) for age-related eye diseases for those living in high-deprivation neighborhoods compared to those living in low-deprivation neighborhoods remained significant after adjustment for potential confounding factors (macular degeneration, OR 1.08, 95% confidence interval, CI, 1.03–1.12; cataract, OR 1.31, 95% CI 1.26–1.35; diabetes-related eye complications, OR 1.36, 95% CI 1.30–1.43; glaucoma, OR 1.11, 95% CI 1.06–1.15). In women, similar patterns were observed (macular degeneration, OR 1.11, 95% CI 1.07–1.15; cataract, OR 1.36, 95% CI 1.31–1.40; diabetes-related eye complications, OR 1.50, 95% CI 1.42–1.59; glaucoma, OR 1.12, 95% CI 1.08–1.17). Conclusion Our results suggest that neighborhood deprivation is associated with age-related eye diseases in both men and women. These results implicate that individual- as well as neighborhood-level factors are important for preventing age-related eye diseases. PMID:26395658

  20. The Role of Complement in Age-Related Macular Degeneration: Heparan Sulphate, a ZIP Code for Complement Factor H?

    PubMed Central

    Langford-Smith, Alex; Keenan, Tiarnan D.L.; Clark, Simon J.; Bishop, Paul N.; Day, Anthony J.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed nations and has been associated with complement dysregulation in the central retina. The Y402H polymorphism in the complement regulatory protein factor H (CFH) can confer a >5-fold increased risk of developing AMD and is present in approximately 30% of people of European descent. CFH, in conjunction with other factors, regulates complement activation in host tissues, and the Y402H polymorphism has been found to alter the protein's specificity for heparan sulphate (HS) – a complex polysaccharide found ubiquitously in mammals. HS, which is present on the cell surface and also in the extracellular matrix, exhibits huge structural diversity due to variations in the level/pattern of sulphation, where particular structures may act as ‘ZIP codes’ for different tissue/cellular locations. Recent work has demonstrated that CFH contains two HS-binding domains that each recognize specific HS ZIP codes, allowing differential recognition of Bruch's membrane (in the eye) or the glomerular basement membrane (in the kidney). Importantly, the Y402H polymorphism impairs the binding of CFH to the HS in Bruch's membrane, which could result in increased complement activation and chronic local inflammation (in 402H individuals) and thereby contribute to AMD pathology. PMID:24335201

  1. Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring.

    PubMed

    Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A; Carter, Anthony J; Alexander, Barbara T

    2016-08-01

    Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

  2. The Factor Structure and Age-Related Factorial Invariance of the Delis-Kaplan Executive Function System (D-KEFS)

    ERIC Educational Resources Information Center

    Latzman, Robert D.; Markon, Kristian E.

    2010-01-01

    There has been an increased interest in the structure of and relations among executive functions.The present study examined the factor structure as well as age-related factorial invariance of the Delis-Kaplan Executive Function System (D-KEFS), a widely used inventory aimed at assessing executive functions. Analyses were first conducted using data…

  3. Nutrigerontology: why we need a new scientific discipline to develop diets and guidelines to reduce the risk of aging-related diseases.

    PubMed

    Verburgh, Kris

    2015-02-01

    Many diets and nutritional advice are circulating, often based on short- or medium-term clinical trials and primary outcomes, like changes in LDL cholesterol or weight. It remains difficult to assess which dietary interventions can be effective in the long term to reduce the risk of aging-related disease and increase the (healthy) lifespan. At the same time, the scientific discipline that studies the aging process has identified some important nutrient-sensing pathways that modulate the aging process, such as the mTOR and the insulin/insulin-like growth factor signaling pathway. A thorough understanding of the aging process can help assessing the efficacy of dietary interventions aimed at reducing the risk of aging-related diseases. To come to these insights, a synthesis of biogerontological, nutritional, and medical knowledge is needed, which can be framed in a new discipline called 'nutrigerontology'. PMID:25470422

  4. Nutrigerontology: why we need a new scientific discipline to develop diets and guidelines to reduce the risk of aging-related diseases

    PubMed Central

    Verburgh, Kris

    2015-01-01

    Many diets and nutritional advice are circulating, often based on short- or medium-term clinical trials and primary outcomes, like changes in LDL cholesterol or weight. It remains difficult to assess which dietary interventions can be effective in the long term to reduce the risk of aging-related disease and increase the (healthy) lifespan. At the same time, the scientific discipline that studies the aging process has identified some important nutrient-sensing pathways that modulate the aging process, such as the mTOR and the insulin/insulin-like growth factor signaling pathway. A thorough understanding of the aging process can help assessing the efficacy of dietary interventions aimed at reducing the risk of aging-related diseases. To come to these insights, a synthesis of biogerontological, nutritional, and medical knowledge is needed, which can be framed in a new discipline called ‘nutrigerontology’. PMID:25470422

  5. Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment

    PubMed Central

    Vavvas, Demetrios G.; Daniels, Anthony B.; Kapsala, Zoi G.; Goldfarb, Jeremy W.; Ganotakis, Emmanuel; Loewenstein, John I.; Young, Lucy H.; Gragoudas, Evangelos S.; Eliott, Dean; Kim, Ivana K.; Tsilimbaris, Miltiadis K.; Miller, Joan W.

    2016-01-01

    Importance Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. Objective We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD. Design Pilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80 mg of atorvastatin daily and were monitored at baseline and every 3 months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women). Results Twenty-three subjects completed a minimum follow-up of 12 months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+ 3.3 letters, p = 0.06) in 10 patients. No subjects progressed to advanced neovascular AMD. Conclusions High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted. PMID:27077128

  6. Vascular endothelial growth factor A polymorphisms and age-related macular degeneration: a systematic review and meta-analysis

    PubMed Central

    Huang, Chen; Xu, Yongsheng; Li, Xuemin

    2013-01-01

    Purpose In the present work, the aim was to systematically review all studies about the association of vascular endothelial growth factor A (VEGF-A) polymorphisms with age-related macular degeneration (AMD) and to perform a meta-analysis. Methods Relevant studies were searched using PubMed, Embase, Wanfang (Chinese), VIP (Chinese), and the Chinese National Knowledge Infrastructure databases up to October, 2011. A meta-analysis was conducted using Stata software, version 11.0. Results A total of nine studies with 2,281 AMD cases and 2,820 controls met our eligibility criteria, and meta-analyses of four polymorphisms of the VEGF-A gene (rs1413711, rs833061, rs2010963, and rs3025039) were performed. This meta-analysis revealed moderate evidence supporting an association between the VEGF-A polymorphisms and AMD. For rs1413711, the TT genotype was associated with an increased risk of overall AMD (TT versus CT model, odds ratio (OR) 1.74, 95% confidence interval (CI) 1.22–2.48) and of wet AMD (TT versus CT model, OR 1.82, 95% CI 1.22–2.71; TT versus (CC+CT) model, OR 1.63, 95% CI 1.13–2.35). For rs833061, the C allele (C allele versus T allele, OR 1.72, 95% CI 1.00–2.96) and CC genotype (CC versus TT model, OR 1.77, 95% CI 1.00–3.11) were the risk factors for overall AMD, while the C allele was also associated with an increased risk of wet AMD (C allele versus T allele, OR 1.54, 95% CI 1.03–2.31). No association was observed between AMD risk and the variant genotypes of VEGF-A rs2010963 and rs3025039 polymorphisms in different genetic models. Conclusions The results suggest the VEGF-A rs1413711 and rs833061 polymorphisms may contribute to AMD susceptibility. PMID:23761723

  7. Bevacizumab (AVASTIN) and age-related macular degeneration. Lower cost does not justify taking risks.

    PubMed

    2015-09-01

    Intravitreal injection of ranibizumab, a VEGF inhibitor, is an option for patients with neovascular age-related macular degeneration (AMD). Because of its lower price, bevacizumab, a VEGF inhibitor closely related to ranibizumab and marketed for the treatment of various malignancies, is sometimes used off label for intravitreal injection in AMD. In 2011, the harm-benefit balance of bevacizumab in patients with AMD was uncertain. New data are available in 2015. In six randomised trials including a total of about 3200 patients, funded independently of the pharmaceutical industry, bevacizumab (1.25 mg per dose) was about as effective as ranibizumab (0.5 mg per injection): visual acuity stabilised or improved in 90% to 95% of patients after one to two years of treatment. During these trials, bevacizumab did not reduce the number of injections needed, as compared with ranibizumab. These trials confirmed the known adverse effect profile of bevacizumab, which is similar to that of ranibizumab and includes serious ocular as well as extraocular adverse effects, in particular cardiac disorders. Serious extraocular adverse events, especially gastrointestinal disorders, were more frequent with bevacizumab than with ranibizumab at one year (18% versus 14%). In early 2015, there are no bevacizumab products suitable for intravitreal injection. In 2011, cases of sight-threatening infectious endophthalmitis were reported in the United States, following contamination during syringe preparation for intravitreal administration. In practice, when treatment with a VEGF inhibitor is considered for AMD, it is more prudent to choose ranibizumab, despite its currently unacceptable price. PMID:26417625

  8. Stimulus and listener factors affecting age-related changes in competing speech perception.

    PubMed

    Helfer, Karen S; Freyman, Richard L

    2014-08-01

    The purpose of this study was to examine associations among hearing thresholds, cognitive ability, and speech understanding in adverse listening conditions within and between groups of younger, middle-aged, and older adults. Participants repeated back sentences played in the presence of several types of maskers (syntactically similar and syntactically different competing speech from one or two other talkers, and steady-state speech-shaped noise). They also completed tests of auditory short-term/working memory, processing speed, and inhibitory ability. Results showed that group differences in accuracy of word identification and in error patterns differed depending upon the number of masking voices; specifically, older and middle-aged individuals had particular difficulty, relative to younger subjects, in the presence of a single competing message. However, the effect of syntactic similarity was consistent across subject groups. Hearing loss, short-term memory, processing speed, and inhibitory ability were each related to some aspects of performance by the middle-aged and older participants. Notably, substantial age-related changes in speech recognition were apparent within the group of middle-aged listeners. PMID:25096109

  9. Hypothesis: cell signalling influences age-related risk of colorectal cancer.

    PubMed

    Bordonaro, Michael; Lazarova, Darina L

    2015-01-01

    We propose that ageing is linked to colonic carcinogenesis through crosstalk between Wnt activity and signalling pathways related to ageing and senescence: progerin, klotho and mTOR. Mutations in the Wnt signalling pathway are responsible for the majority of colorectal cancers (CRCs); however, hyperactivation of Wnt signalling by butyrate, a breakdown product of dietary fibre, induces CRC cell apoptosis. This effect of butyrate may in part explain the protective action of fibre against CRC. Hutchinson-Gilford progeria syndrome is a premature ageing disorder caused by accumulation of the progerin protein; however, healthy individuals also produce progerin in the course of their normal ageing. Progerin activates expression of the Wnt inhibitors HES1 and TLE1. Thus, we hypothesize that with age, the increasing expression of progerin suppresses butyrate-mediated Wnt hyperactivation and apoptosis, leading to increased CRC risk. Wild-type klotho contributes to a significantly increased lifespan; however, Klotho gene variants differ significantly between newborns and elderly. Klotho inhibits basal Wnt signalling activity; thus, the protein may function as a tumour suppressor for CRC. However, similar to progerin, klotho variants associated with lifespan differences may repress butyrate-mediated Wnt hyperactivation, and thus increase the risk of CRC. Finally, mTOR signalling has also been linked to human ageing, and crosstalk between Wnt and mTOR signalling may influence colonic tumourigenesis. Understanding how progerin, klotho and mTOR link ageing with colonic neoplastic development may lead to novel preventive and therapeutic strategies against CRC associated with age. PMID:25388238

  10. Involvement of genetic factors in the response to a variable-dosing ranibizumab treatment regimen for age-related macular degeneration

    PubMed Central

    Nowinska, Anna; Pilat, Jaroslaw; Palucha, Andrzej; Wylegala, Edward

    2010-01-01

    Purpose To determine whether gene polymorphisms of the major genetic risk factor for age-related macular susceptibility 2 (ARMS2 A69S) and the complement factor H Y402H influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration. Methods This prospective cohort study included 90 patients (90 eyes) with exudative age related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (Mitchell et al.). Injections were administered monthly when a patient lost five letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness (CSRT). Genotypes (rs10490924 and rs1061170) were analyzed using gene sequence analysis. Best-corrected visual acuity (BCVA) and CSRT values were compared between ARMS2 and complement factor H genotypes. Multiple regression analysis was used to assess the statistical significance. Results Mean increase in visual acuity was 4.44±8.12 letters with a 103.63±94.7 µm decrease in CSRT. BCVA improvement was statistically significant in all genotype groups except in homozygous 69S in the AMRS2 gene. CSRT and BCVA changes were correlated (r=0.2521; 95% CI: 0.04746–0.4364, p=0.0165). Multiple regression analysis revealed a significant impact of 69S (p=0.015) on the change in BCVA. Conclusions Visual acuity did not improve during the study in patients homozygous for ARMS2 69S, despite a decrease in CSRT. Further investigation is needed to confirm our findings and understand the mechanisms involved. PMID:21151600

  11. Growth and Age-Related Abnormalities in Cortical Structure and Fracture Risk.

    PubMed

    Seeman, Ego

    2015-12-01

    Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from 'within.' Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay in vivo. The challenges still to be met are to determine whether measurement of porosity identifies persons at risk for fracture, whether this approach is compliments information obtained using bone densitometry, and whether changes in cortical porosity and other microstructural traits have the sensitivity to serve as surrogates of treatment success or failure. PMID:26394727

  12. Growth and Age-Related Abnormalities in Cortical Structure and Fracture Risk

    PubMed Central

    2015-01-01

    Vertebral fractures and trabecular bone loss have dominated thinking and research into the pathogenesis and the structural basis of bone fragility during the last 70 years. However, 80% of all fractures are non-vertebral and occur at regions assembled using large amounts of cortical bone; only 20% of fractures are vertebral. Moreover, ~80% of the skeleton is cortical and ~70% of all bone loss is cortical even though trabecular bone is lost more rapidly than cortical bone. Bone is lost because remodelling becomes unbalanced after midlife. Most cortical bone loss occurs by intracortical, not endocortical remodelling. Each remodelling event removes more bone than deposited enlarging existing canals which eventually coalesce eroding and thinning the cortex from 'within.' Thus, there is a need to study the decay of cortical as well as trabecular bone, and to develop drugs that restore the strength of both types of bone. It is now possible to accurately quantify cortical porosity and trabecular decay in vivo. The challenges still to be met are to determine whether measurement of porosity identifies persons at risk for fracture, whether this approach is compliments information obtained using bone densitometry, and whether changes in cortical porosity and other microstructural traits have the sensitivity to serve as surrogates of treatment success or failure. PMID:26394727

  13. High concentrations of plasma n3 fatty acids are associated with decreased risk for late age-related macular degeneration.

    PubMed

    Merle, Bénédicte M J; Delyfer, Marie-Noëlle; Korobelnik, Jean-François; Rougier, Marie-Bénédicte; Malet, Florence; Féart, Catherine; Le Goff, Mélanie; Peuchant, Evelyne; Letenneur, Luc; Dartigues, Jean-François; Colin, Joseph; Barberger-Gateau, Pascale; Delcourt, Cécile

    2013-04-01

    High dietary intakes of n3 (ω3) polyunsaturated fatty acids (PUFA) and fish have been consistently associated with a decreased risk for age-related macular degeneration (AMD). We assessed the associations of late AMD with plasma n3 PUFA, a nutritional biomarker of n3 PUFA status. The Antioxydants Lipides Essentiels Nutrition et Maladies Occulaires (Alienor) Study is a prospective, population-based study on nutrition and age-related eye diseases performed in 963 residents of Bordeaux (France) aged ≥73 y. Participants had a first eye examination in 2006-2008 and were followed for 31 mo on average. Plasma fatty acids were measured by GC from fasting blood samples collected in 1999-2001. AMD was graded from non-mydriatic color retinal photographs at all examinations and spectral domain optical coherence tomography at follow-up. After adjustment for age, gender, smoking, education, physical activity, plasma HDL-cholesterol, plasma triglycerides, CFH Y402H, apoE4, and ARMS2 A69S polymorphisms, and follow-up time, high plasma total n3 PUFA was associated with a reduced risk for late AMD [OR = 0.62 for 1-SD increase (95% CI: 0.44-0.88); P = 0.008]. Associations were similar for plasma 18:3n3 [OR = 0.62 (95% CI: 0.43-0.88); P = 0.008] and n3 long-chain PUFA [OR = 0.65 (95% CI: 0.46-0.92); P = 0.01]. This study gives further support to the potential role of n3 PUFAs in the prevention of late AMD and highlights the necessity of randomized clinical trials to determine more accurately the value of n3 PUFAs as a means of reducing AMD incidence. PMID:23406618

  14. Inherited catalase deficiency: is it benign or a factor in various age related disorders?

    PubMed

    Góth, László; Nagy, Teréz

    2013-01-01

    Hydrogen peroxide was - and is still - considered toxic for a wide range of living organisms. Oxidative stress occurs when there is an excess of pro-oxidants over antioxidants and it has been implicated in several diseases. Catalase is involved in hydrogen peroxide catabolism and is important in defense against oxidative stress. Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase. Acatalasemia was thought at first to be an asymptotic disorder. In the absence of catalase, neither the Japanese, or Hungarian acatalasemics nor acatalasemic mice had significantly increased blood glutathione peroxidase activity. In animal models, catalase deficient tissues show much slower rates of removal of extracellular hydrogen peroxide. In catalase knock-out mice, a decreased hydrogen peroxide removing capacity and increased reactive oxygen species formation were reported. Hydrogen peroxide may cause methemoglobinemia in patients with catalase deficiency. During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia. Patients with inherited catalase deficiency, who are treated with uric acid oxidase (rasburicase) may experience very high concentrations of hydrogen peroxide and may suffer from methemoglobinemia and hemolysis. The high (18.5%) prevalence of diabetes mellitus in inherited catalase deficient individuals and the earlier (10 years) manifestation of the disease may be attributed to the oxidative damage of oxidant sensitive, insulin producing pancreatic beta-cells. Ninety-seven of 114 acatalasemics had diseases related to oxidative stress and aging. The oxidative stress due to catalase deficiency could contribute to the manifestation of diabetes while for the other diseases it may be one of the factors in their causations. In summary, inherited catalase deficiency is associated with clinical features, pathologic laboratory test results

  15. No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort

    PubMed Central

    Chen, Jian-Huan; Yang, Yunli; Zheng, Yuqian; Qiu, Minghui; Xie, Mingliang; Lin, Wenjie; Zhang, Mingzhi; Pang, Chi Pui

    2013-01-01

    Purpose Single nucleotide polymorphisms (SNPs) of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 (ARMS2/HTRA1) and complement factor H (CFH) have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of ARMS2/HTRA1 and CFH SNPs with early age-related maculopathy (ARM) in a Han Chinese cohort. Methods The cohort consisted of 315 unrelated subjects, including 158 patients with early ARM and 157 recruited controls. Early ARM was diagnosed and graded according to the Age-Related Eye Disease Study criteria. Four SNPs in ARMS2/HTRA1 and six SNPs in CFH previously reported to be associated with AMD were genotyped using TaqMan genotyping assays. Logistic regression implemented with the R statistical language was used for association analysis. Results None of the ARMS2/HTRA1 and CFH SNPs showed any significant association with early ARM (all p>0.453), with the odds ratios ranging from 0.88 to 1.17. None of the SNPs were associated with unilateral or bilateral early ARM or any grade of early ARM (all p>0.249). Conclusions The association of ARMS2/HTRA1 and CFH SNPs in early ARM was not detected in our cohort. The findings in the current study indicated that the effects of ARMS2/HTRA1 and CFH in early ARM could be much lower compared to those in AMD. PMID:23687431

  16. Are age-related trends in suicide rates associated with life expectancy and socio-economic factors?

    PubMed

    Shah, Ajit

    2009-01-01

    Background. A recent cross-national study reported that suicide rates increased, decreased or remained unchanged with increasing age in individual countries. The relationship between age-related trends in suicide rates and child mortality rates, life expectancy and socio-economic factors was examined. Methods. Countries with an increase, decrease and no change in suicide rates with increasing age were ascertained from an earlier study (Shah, 2007a, International Psychogeriatrics, 19, 1141), which analysed data from the World Health Organisation (WHO). The relationship between age-related trends in suicide rates and (i) child mortality rates, (ii) life expectancy and (iii) markers of socio-economic status (per capita gross national domestic product (GDP) and the Gini coeffcient) was examined using data from the WHO and the United Nations. Results. The main findings were: (i) child mortality rates were significantly lower in countries with an increase in suicide rates with increasing age when compared to countries without a change in suicide rates with increasing age in males; (ii) life expectancy was significantly higher in countries with an increase in suicide rates with increasing age when compared to countries without a change in suicide rates with increasing age in males; and (iii) the Gini coefficient was significantly lower in countries with an increase in suicide rates with increasing age when compared to countries without a change or a decline in suicide rates with increasing age in females. Conclusions. Potential explanations for these findings and the interaction of life expectancy and socio-economic factors with other factors that differentially influence suicide rates in different age and sex groups requires further examination. PMID:24946117

  17. Homocysteine and the risk of age-related macular degeneration: a systematic review and meta-analysis

    PubMed Central

    Huang, Peirong; Wang, Fenghua; Kumar Sah, Birendra; Jiang, Junhai; Ni, Zhentian; Wang, Jentso; Sun, Xiaodong

    2015-01-01

    Contrasting results have been reported regarding the associations between plasma total homocysteine (tHcy) and B vitamin levels and age-related macular degeneration (AMD) risk. Thus, we aimed to systematically evaluate these associations. Relevant case control studies in English were identified via a thorough search of the PubMed, Medline, and Embase databases from inception to June 2014. The results were pooled using Review Manager 5.2.1. Eleven studies (including 1072 cases and 1202 controls) were eligible for analysis of tHcy levels; additionally, 3 studies (including 152 cases and 98 controls) were eligible for analysis of folic acid and vitamin B12 levels. The cumulative results demonstrated that the plasma tHcy level among the AMD cases was 2.67 μmol/L (95% confidence interval [CI], 1.60-3.74) higher than that among the controls. In contrast, the vitamin B12 level among the AMD cases was 64.16 pg/mL (95% CI, 19.32-109.00) lower than that among the controls. Subgroup analyses showed that the folic acid level was 1.66 ng/mL (95% CI, 0.10-3.21) lower for the wet type. Together, the results demonstrated that AMD is associated with elevated tHcy levels and decreased vitamin B12 levels. Plasma tHcy may act as a modulator of the risk for AMD based on the current evidence. PMID:26194346

  18. Relationship between SERPING1 rs2511989 polymorphism and age-related macular degeneration risk: A meta-analysis

    PubMed Central

    Ma, Yan-Bo; Fu, Shao-Ying; Ma, Yan-Hua

    2014-01-01

    Purpose We conducted a meta-analysis aiming to evaluate the relationship between a common polymorphism (rs2511989 G>A) in the SERPING1 gene and the risk of age-related macular degeneration (AMD). Methods The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1, 2013, without any language restrictions. A meta-analysis was conducted using STATA 12.0 software. We calculated a crude odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the relationships under five genetic models. Results Seven case-control studies with a total of 7,159 patients with AMD and 5,797 healthy subjects met the inclusion criteria. The results of our meta-analysis showed that the SERPING1 rs2511989 polymorphism might be correlated with an increased risk of AMD (G allele versus A allele: OR = 1.09, 95% CI = 1.03–1.15, p = 0.020; GG + GA versus AA: OR = 1.14, 95% CI = 1.03–1.26, p = 0.014; GG versus GA+AA: OR = 1.10, 95% CI = 1.02–1.19, p = 0.012; GG versus AA: OR = 1.20, 95% CI = 1.07–1.34, p = 0.002; respectively). Results of subgroup analysis by ethnicity revealed positive correlations between the SERPING1 rs2511989 polymorphism and risk of AMD among Caucasians under five genetic models (all p<0.05), but not among Asians (all p>0.05). Conclusions The current meta-analysis shows that the SERPING1 rs2511989 polymorphism may have a positive effect on the risk of AMD, especially among Caucasians. PMID:25352749

  19. Complement Factor H Y402H and LOC387715 A69S Polymorphisms in Association with Age-Related Macular Degeneration in Iran

    PubMed Central

    Nazari Khanamiri, Hossein; Ghasemi Falavarjani, Khalil; Sanati, Mohammad Hossein; Aryan, Hajar; Irani, Alireza; Hashemi, Masih; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Nikeghbali, Aminollah

    2014-01-01

    Purpose To determine the frequency of complement factor H (Y402H) and age related macular degeneration susceptibility gene 2 (A69S) single nucleotide polymorphisms in patients with age-related macular degeneration (AMD) and in matched non-AMD controls in an Iranian population. Methods Seventy patients with AMD and 86 age- and sex-matched controls were recruited and examined. Peripheral blood sample was obtained from all subjects for DNA extraction and direct sequencing of Y402H and A69S genes. Odds ratios (ORs) with 95% confidence intervals (CIs) for the association of Y402H and A69S polymorphisms with AMD were determined. Results The frequencies of both homozygous and heterozygous genotypes were significantly higher in cases than controls for both Y402H and A69S polymorphisms. In comparison to the wild genotypes, OR for AMD associated with Y402H and A69S polymorphisms were 1.9 (95% CI, 1.1-3.2) and 2.2 (95%CI, 1.6-3.1), respectively. Joint risk analysis considering both genes revealed a higher risk of AMD when polymorphisms were present for both genes. Conclusion Y402H and A69S polymorphisms were strongly associated with AMD in this Iranian population. PMID:25279119

  20. Expression of Human Complement Factor H Prevents Age-Related Macular Degeneration–Like Retina Damage and Kidney Abnormalities in Aged Cfh Knockout Mice

    PubMed Central

    Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B.; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G.; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M.; Bowes Rickman, Catherine

    2016-01-01

    Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh−/−) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh−/− mice, and transgenics had a thicker outer nuclear layer and less sub–retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets. PMID:25447048

  1. Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study.

    PubMed

    Gee, Dylan G; Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Lieberman, Matthew D; Belger, Aysenil; Perkins, Diana O; Olvet, Doreen M; Cornblatt, Barbara A; Constable, Todd; Woods, Scott W; Addington, Jean; Cadenhead, Kristin S; McGlashan, Thomas H; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Cannon, Tyrone D

    2012-01-01

    Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning. PMID:22056201

  2. Risk Factors

    MedlinePlus

    ... has been linked to some cancers: Links between air pollution and cancer risk have been found. These include ... between lung cancer and secondhand tobacco smoke , outdoor air pollution, and asbestos . Drinking water that contains a large ...

  3. Risk Factors

    MedlinePlus

    ... heart disease and stroke. However, certain groups—including African Americans and older individuals—are at higher risk ... life expectancy found among minorities. As of 2007, African American men were 30% more likely to die ...

  4. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

  5. Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians

    PubMed Central

    Gharib, Amal F.; Dabour, Sherif A.; Fouad, Rania A.

    2014-01-01

    Purpose To analyze the association of the polymorphisms of xeroderma pigmentosum complementation group D (XPD) and 8-oxoguanine glycosylase-1 (OGG1) genes with the risk of age-related cataract (ARC) in an Egyptian population. Methods This case-control study included 150 patients with ARC and 50 controls. Genotyping of XPD Asp312Asn was performed by amplification refractory mutation system PCR assay and genotyping of OGG1 Ser326Cys was carried out by PCR including confronting two-pair primers. Results The Asn/Asn genotype of XPD gene was significantly associated with increased risk of ARC (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.01–7.43, p = 0.04) and cortical cataract (OR = 5.06, 95% CI = 1.70–15.05, p = 0.002). The Asn312 allele was significantly associated with an increased risk of ARC (OR = 1.75, 95% CI 1.06–2.89, p = 0.03) and cortical cataract (OR = 2.81, 95% CI = 1.56–5.08, p<0.001). The OGG1 Cys/Cys genotype frequency was significantly higher in ARC (OR = 4.13, 95% CI = 0.93–18.21, p = 0.04) and the Cys326 allele (OR = 1.85, 95% CI = 1.07–3.20, p = 0.03). Moreover, the Cys/Cys genotype of the OGG1 gene was significantly higher in cortical cataract (OR = 6.00, 95% CI = 1.24–28.99, p = 0.01) and the Cys326 allele was also significantly associated with cortical cataract (OR = 2.45, 95% CI = 1.30–4.63, p = 0.005). Conclusions The results suggest that the Asn/Asn genotype and Asn312 allele of XPD polymorphism, as well as the Cys/Cys genotype and Cys326 allele of the OGG1 polymorphism, may be associated with increased risk of the development of ARC, particularly the cortical type, in the Egyptian population. PMID:24868140

  6. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

    Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC. PMID:21876810

  7. Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration

    PubMed Central

    Kopplin, Laura J; Igo, Robert P; Wang, Yang; Sivakumaran, Theru A; Hagstrom, Stephanie A; Peachey, Neal S; Francis, Peter J; Klein, Michael L; SanGiovanni, John Paul; Chew, Emily Y; Pauer, Gayle JT; Sturgill, Gwen M; Joshi, Tripti; Tian, Liping; Xi, Quansheng; Henning, Alice K; Lee, Kristine E.; Klein, Ronald; Klein, Barbara EK; Iyengar, Sudha K

    2011-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case/control cohort. We tested the top findings for replication in 1 896 cases and 1 866 controls and identified two novel genetic protective factors for AMD. In addition to the CFH (p=2.3×10−64) and ARMS2 (p=1.2×10−60) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (p=5.3×10−15), a gene near the C2/BF locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (p=2.9×10−4), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3. PMID:20861866

  8. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  9. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration.

    PubMed

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L; Kamei, Motohiro

    2012-05-15

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  10. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration

    PubMed Central

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L.; Kamei, Motohiro

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  11. Prognostic factors of early morphological response to treatment with ranibizumab in patients with wet age-related macular degeneration.

    PubMed

    Chrapek, Oldřich; Jarkovský, Jiří; Šín, Martin; Studnička, Jan; Kolář, Petr; Jirková, Barbora; Dušek, Ladislav; Pitrová, Šárka; Řehák, Jiří

    2015-01-01

    Aim. To assess the significance of age, gender, baseline best corrected visual acuity, baseline macula thickness, and type and size of choroidal neovascularization in early morphological therapeutic response to ranibizumab treatment in patients with the wet form of age-related macular degeneration. Methods. From 09/2008 to 06/2013 we evaluated 1153 newly diagnosed, treatment-naïve patients treated with ranibizumab. Based on the morphological findings in the macula following the initial 3 injections of ranibizumab, the patients were divided into two groups based on active and inactive choroidal neovascularization. Results. After the initial 3 injections of ranibizumab, we examined the sample of 841 eyes with active CNV and 312 eyes with inactive CNV. In the inactive group, we found a statistically higher proportion of occult CNV (P < 0.001) and lower incidence of CNV greater than 5DA (P < 0.001) compared with the active group. We found no statistically significant difference in age, gender, baseline best corrected visual acuity, or baseline macula thickness between the inactive and active groups. Conclusion. Occult CNV and CNV smaller than 5DA are optimistic factors for a better morphological therapeutic response at the beginning of ranibizumab treatment. PMID:25821593

  12. Oxidative Stress and the Nrf2 Anti-Oxidant Transcription Factor in Age-Related Macular Degeneration.

    PubMed

    Lambros, Mandy L; Plafker, Scott M

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of acquired and irreversible blindness among elderly Americans. Most AMD patients have the dry form of the disease (dAMD) for which reliable therapies are lacking. A major obstacle to the development of effective treatments is a deficit in our understanding of what triggers dAMD onset. This is particularly the case with respect to the events that cause retinal pigment epithelial (RPE) cells to transition from a state of health and homeostasis to one of dysfunction and atrophy. These cells provide critical support to the photoreceptors and their atrophy often precipitates photoreceptor death in dAMD. Chronic oxidative stress is a primary driver of age-dependent, RPE atrophy. Sources of this stress have been identified (e.g., cigarette smoke, photooxidized bisretinoids), but we still do not understand how these stressors damage RPE constituents or what age-dependent changes undermine the cytoprotective systems in the RPE. This review focuses on Nrf2, the master antioxidant transcription factor, and its role in the RPE during aging and dAMD onset. PMID:26427395

  13. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  14. Expression Analysis of an Evolutionarily Conserved Alternative Splicing Factor, Sfrs10, in Age-Related Macular Degeneration

    PubMed Central

    Karunakaran, Devi Krishna Priya; Banday, Abdul Rouf; Wu, Qian; Kanadia, Rahul

    2013-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population. Hypoxic stress created in the micro-environment of the photoreceptors is thought to be the underlying cause that results in the pathophysiology of AMD. However, association of AMD with alternative splicing mediated gene regulation is not well explored. Alternative Splicing is one of the primary mechanisms in humans by which fewer protein coding genes are able to generate a vast proteome. Here, we investigated the expression of a known stress response gene and an alternative splicing factor called Serine-Arginine rich splicing factor 10 (Sfrs10). Sfrs10 is a member of the serine-arginine (SR) rich protein family and is 100% identical at the amino acid level in most mammals. Immunoblot analysis on retinal extracts from mouse, rat, and chicken showed a single immunoreactive band. Further, immunohistochemistry on adult mouse, rat and chicken retinae showed pan-retinal expression. However, SFRS10 was not detected in normal human retina but was observed as distinct nuclear speckles in AMD retinae. This is in agreement with previous reports that show Sfrs10 to be a stress response gene, which is upregulated under hypoxia. The difference in the expression of Sfrs10 between humans and lower mammals and the upregulation of SFRS10 in AMD is further reflected in the divergence of the promoter sequence between these species. Finally, SFRS10+ speckles were independent of the SC35+ SR protein speckles or the HSF1+ stress granules. In all, our data suggests that SFRS10 is upregulated and forms distinct stress-induced speckles and might be involved in AS of stress response genes in AMD. PMID:24098751

  15. The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population.

    PubMed

    Luo, Huajie; Wu, Hao; Shen, Hailian; Chen, Haifeng; Yang, Tao; Huang, Zhiwu; Jin, Xiaojie; Pang, Xiuhong; Li, Lei; Hu, Xianting; Jiang, Xuemei; Fan, Zhuping; Li, Jiping

    2016-07-01

    This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals. PMID:26187738

  16. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956

  17. A prospective study of common variants in the RAR-related orphan receptor alpha (RORalpha) gene and risk of neovascular age-related macular degeneration

    PubMed Central

    Schaumberg, Debra A.; Chasman, Daniel; Morrison, Margaux A.; Adams, Scott M.; Guo, Qun; Hunter, David J.; Hankinson, Susan E.; DeAngelis, Margaret M.

    2010-01-01

    Objectives The RAR-related orphan receptor alpha (RORalpha) gene is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and two clinic-based cross sectional studies. We aimed to determine if common variants in RORalpha predict future risk of neovascular AMD. Methods We measured genotypes for 18 variants in intron 1 of the RORalpha gene among 164 cases who developed neovascular AMD and 485 age- and sex-matched controls in a prospective nested case-control study within the Nurses’ Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios (IRR) and 95% confidence intervals (CI) for neovascular AMD for each variant, and examined interactions with other AMD-associated variants and modifiable risk factors. Results We identified a single SNP (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with one and two copies of the “G” allele were 1.73 (CI= 1.32–2.27) and 2.99 (CI=1.74–5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the “G” allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascular AMD (CI=10.1–164; P for interaction=0.017). Cigarette smokers who carried two copies of the “G” allele had a 9.89-fold risk of neovascular AMD, but the interaction was not significant (P=0.08). We identified a significant AMD-associated haplotype block containing SNPs rs730754, rs8034864, and rs12900948, with P-values for ACA=1.16 × 10−9, ACG=5.85 × 10−12, and GAA=0.0001 when compared to all other haplotypes. Conclusion Common variants and haplotypes within the RORalpha gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should

  18. The Difference that Age Makes: Cultural Factors that Shape Older Adults' Responses to Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Mogk, Marja

    2008-01-01

    This article suggests that approaching vision loss from age-related macular degeneration from a sociocultural perspective, specifically considering perceptions of aging, blindness, disability, and generational viewpoints and norms, may be critical to understanding older adults' responses to vision loss and visual rehabilitation.

  19. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  20. Identification of factor H-like protein 1 as the predominant complement regulator in Bruch’s membrane: implications for age-related macular degeneration

    PubMed Central

    Clark, Simon J.; Schmidt, Christoph Q.; White, Anne M.; Hakobyan, Svetlana; Morgan, B. Paul; Bishop, Paul N.

    2014-01-01

    The tight regulation of innate immunity on extracellular matrix (ECM) is a vital part of immune homeostasis throughout the human body and disruption to this regulation in the eye is thought to contribute directly to the progression of age-related macular degeneration (AMD). The plasma complement regulator factor H (FH) is believed to be the main regulator that protects ECM against damaging complement activation. However, here we demonstrate that a truncated form of FH, called factor-H like protein 1 (FHL-1), is the main regulatory protein in the layer of ECM under human retina, called Bruch’s membrane. Bruch’s membrane is a major site of AMD disease pathogenesis and where drusen, the hallmark lesions of AMD, form. We show that FHL-1 can passively diffuse through Bruch’s membrane, whereas the full sized, glycosylated, FH cannot. FHL-1 is largely bound to Bruch’s membrane through interactions with heparan sulfate and we show that the common Y402H polymorphism in the CFH gene, associated with an increased risk of AMD, reduces the binding of FHL-1 to this heparan sulfate. We also show that FHL-1 is retained in drusen while FH coats the periphery of the lesions, perhaps inhibiting their clearance. Our results identify a novel mechanism of complement regulation in the human eye, which highlights potential new avenues for therapeutic strategies. PMID:25305316

  1. Relationship between Systemic Cytokines and Complement Factor H Y402H Polymorphism in Patients With Dry Age-Related Macular Degeneration

    PubMed Central

    CAO, SIJIA; KO, ASHLEY; PARTANEN, MARITA; PAKZAD-VAEZI, KAIVON; MERKUR, ANDREW B.; ALBIANI, DAVID A.; KIRKER, ANDREW W.; WANG, AIKUN; CUI, JING Z.; FOROOGHIAN, FARZIN; MATSUBARA, JOANNE A.

    2014-01-01

    PURPOSE To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD). DESIGN Cross-sectional study. METHODS Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons. RESULTS The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P < .01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor α than those with the CT variants, the TT variant, or both (P < .01). Interleukin-1β did not reach significance (P = .02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P >.15). CONCLUSIONS The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology. PMID:24083687

  2. Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis

    PubMed Central

    Wei, Li; Han, Ya-di; Cui, Ning-hua; Huang, Zhu-liang; Li, Zu-hua; Zheng, Fang; Yan, Ming

    2015-01-01

    Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by

  3. Multifactor Effects and Evidence of Potential Interaction between Complement Factor H Y402H and LOC387715 A69S in Age-Related Macular Degeneration

    PubMed Central

    Seitsonen, Sanna P.; Onkamo, Päivi; Peng, Gang; Xiong, Momiao; Tommila, Petri V.; Ranta, Päivi H.; Holopainen, Juha M.; Moilanen, Jukka A.; Palosaari, Tapani; Kaarniranta, Kai; Meri, Seppo; Immonen, Ilkka R.; Järvelä, Irma E.

    2008-01-01

    Background Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. Methods/Principal Findings We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75×10−9; non-AMD controls and OR 2.79, p = 2.78×10−19, blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. Conclusions/Significance Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index. PMID:19048105

  4. Age-Related Macular Degeneration-Associated Silent Polymorphisms in HtrA1 Impair Its Ability To Antagonize Insulin-Like Growth Factor 1

    PubMed Central

    Jacobo, Sarah Melissa P.; DeAngelis, Margaret M.; Kim, Ivana K.

    2013-01-01

    Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD. PMID:23478260

  5. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy*

    PubMed Central

    Ebert, Scott M.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.; Murry, Daryl J.; Fox, Daniel K.; Bongers, Kale S.; Lira, Vitor A.; Meyerholz, David K.; Talley, John J.; Adams, Christopher M.

    2015-01-01

    Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality, and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle. PMID:26338703

  6. Identification and Small Molecule Inhibition of an Activating Transcription Factor 4 (ATF4)-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy.

    PubMed

    Ebert, Scott M; Dyle, Michael C; Bullard, Steven A; Dierdorff, Jason M; Murry, Daryl J; Fox, Daniel K; Bongers, Kale S; Lira, Vitor A; Meyerholz, David K; Talley, John J; Adams, Christopher M

    2015-10-16

    Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality, and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle. PMID:26338703

  7. Calcium, calcification, and melatonin biosynthesis in the human pineal gland: a postmortem study into age-related factors.

    PubMed

    Schmid, H A; Requintina, P J; Oxenkrug, G F; Sturner, W

    1994-05-01

    It is believed that pineal calcification may be age-associated and that the well-demonstrated age-related decline in melatonin biosynthesis may be an expression of an alteration in calcium homeostasis in the pinealocyte. Prior correlations of melatonin to calcium deposition and age were made on the basis of radiological or semiquantitative analysis. In this postmortem study of 33 subjects (age range 3 months to 65 years) calcium deposits measured by atomic absorption spectrometry correlated positively with age in day and night samples (day: r = 0.56, P < 0.05; night: r = 0.818, P < 0.001). Nighttime (2200 h to 0800 h) pineal melatonin content (HPLC fluorometry) was higher than daytime melatonin levels (nighttime 3.80 +/- 0.3 vs. daytime 0.85 +/- 0.4 ng/mg protein). Nighttime calcium levels in the supernatant correlated negatively with melatonin content (r = -0.59, P < 0.05). PMID:7807371

  8. Novel risk index for the identification of age-related macular degeneration using radon transform and DWT features.

    PubMed

    Acharya, U Rajendra; Mookiah, Muthu Rama Krishnan; Koh, Joel E W; Tan, Jen Hong; Noronha, Kevin; Bhandary, Sulatha V; Rao, A Krishna; Hagiwara, Yuki; Chua, Chua Kuang; Laude, Augustinus

    2016-06-01

    Age-related Macular Degeneration (AMD) affects the central vision of aged people. It can be diagnosed due to the presence of drusen, Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in the fundus images. It is labor intensive and time-consuming for the ophthalmologists to screen these images. An automated digital fundus photography based screening system can overcome these drawbacks. Such a safe, non-contact and cost-effective platform can be used as a screening system for dry AMD. In this paper, we are proposing a novel algorithm using Radon Transform (RT), Discrete Wavelet Transform (DWT) coupled with Locality Sensitive Discriminant Analysis (LSDA) for automated diagnosis of AMD. First the image is subjected to RT followed by DWT. The extracted features are subjected to dimension reduction using LSDA and ranked using t-test. The performance of various supervised classifiers namely Decision Tree (DT), Support Vector Machine (SVM), Probabilistic Neural Network (PNN) and k-Nearest Neighbor (k-NN) are compared to automatically discriminate to normal and AMD classes using ranked LSDA components. The proposed approach is evaluated using private and public datasets such as ARIA and STARE. The highest classification accuracy of 99.49%, 96.89% and 100% are reported for private, ARIA and STARE datasets. Also, AMD index is devised using two LSDA components to distinguish two classes accurately. Hence, this proposed system can be extended for mass AMD screening. PMID:27107676

  9. Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy?

    PubMed Central

    Fernández-Vega, Beatriz; Fernández-Vega, Álvaro; Rangel, Carlos Mario; Nicieza, Javier; Villota-Deleu, Eva; Vega, José A.; Sanchez-Avila, Ronald M.

    2016-01-01

    Aims To report a case of wet age-related macular degeneration (wet-AMD) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) drug, for concomitant Crohn's disease. Methods Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment). Best-corrected visual acuity (BCVA) was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg) for a period of 40 months with intervals of 1–6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks). During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes. PMID:27065854

  10. Change of retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in exudative age-related macular degeneration

    PubMed Central

    Kim, Moosang; Kim, Eung Suk; Seo, Kyung Hoon; Yu, Seung-Young; Kwak, Hyung-Woo

    2016-01-01

    Purpose: The study aimed to investigate the quantitative changes of retinal pigment epithelial (RPE) atrophy during a 24-month follow-up period of anti-vascular endothelial growth factor (VEGF) for exudative age-related macular degeneration (AMD). Materials and Methods: This is a retrospective study. Sixty-five eyes of 62 consecutive patients with naïve exudative AMD who had received treatment with anti-VEGF therapy and followed for more 24 months were enrolled. All patients received three initial monthly injections of anti-VEGF (ranibizumab or bevacizumab), followed by pro re nata or treat-and-extend protocol. Color fundus image, optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was performed to investigate the predictive factors found during univariate analysis to identify an association with increased RPE atrophic areas. Results: The mean number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 ± 1.298 mm2 at baseline and enlarged to 2.394 ± 1.940 mm2 after 24 months, which differed significantly (P = 0.001). Multiple regression analysis revealed that larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments were associated with increased RPE atrophic areas. Conclusions: RPE atrophy progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated with an increased risk of progression of RPE atrophy the following treatment. These findings may be useful to clinicians using intravitreal anti-VEGF for the treatment of exudative AMD, both for selecting an appropriate treatment plan and for predicting the progression of RPE atrophy. PMID:27488150

  11. Heart disease - risk factors

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000106.htm Heart disease - risk factors To use the sharing features on this ... may help you live a longer, healthier life. Risk Factors You Cannot Change Some of your heart ...

  12. Refractive Error and Risk of Early or Late Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Ying; Wang, JiWen; Zhong, XiaoJing; Tian, Zhen; Wu, Peipei; Zhao, Wenbo; Jin, Chenjin

    2014-01-01

    Objective To summarize relevant evidence investigating the associations between refractive error and age-related macular degeneration (AMD). Design Systematic review and meta-analysis. Methods We searched Medline, Web of Science, and Cochrane databases as well as the reference lists of retrieved articles to identify studies that met the inclusion criteria. Extracted data were combined using a random-effects meta-analysis. Studies that were pertinent to our topic but did not meet the criteria for quantitative analysis were reported in a systematic review instead. Main outcome measures Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between refractive error (hyperopia, myopia, per-diopter increase in spherical equivalent [SE] toward hyperopia, per-millimeter increase in axial length [AL]) and AMD (early and late, prevalent and incident). Results Fourteen studies comprising over 5800 patients were eligible. Significant associations were found between hyperopia, myopia, per-diopter increase in SE, per-millimeter increase in AL, and prevalent early AMD. The pooled ORs and 95% CIs were 1.13 (1.06–1.20), 0.75 (0.56–0.94), 1.10 (1.07–1.14), and 0.79 (0.73–0.85), respectively. The per-diopter increase in SE was also significantly associated with early AMD incidence (OR, 1.06; 95% CI, 1.02–1.10). However, no significant association was found between hyperopia or myopia and early AMD incidence. Furthermore, neither prevalent nor incident late AMD was associated with refractive error. Considerable heterogeneity was found among studies investigating the association between myopia and prevalent early AMD (P = 0.001, I2 = 72.2%). Geographic location might play a role; the heterogeneity became non-significant after stratifying these studies into Asian and non-Asian subgroups. Conclusion Refractive error is associated with early AMD but not with late AMD. More large-scale longitudinal studies are needed to further investigate such

  13. Association between complementary factor H Y402H polymorphisms and age-related macular degeneration in Chinese: Systematic review and meta-analysis

    PubMed Central

    Quan, Yan-Long; Zhou, Ai-Yi; Feng, Zhao-Hui

    2012-01-01

    AIM Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associate with the AMD. To investigate whether the Y402H variant in CFH is associated with AMD in Chinese populations, a systematic review and meta-analysis were performed to estimate the magnitude of the gene effect and the possible mode of action. METHODS A meta-analysis was performed using data available from ten case-control studies assessing association between the CFH Y402H polymorphism and AMD in Chinese populations involving 1538 AMD. Data extraction and study quality assessment were performed in duplicate. Summary odds ratios (ORs) and 95% confidence intervals (CIs) an allele contrast and genotype contrast were estimated using fixed- effects models. The Q-statistic test was used to assess heterogeneity, and Funnel plot was used to evaluate publication bias. RESULTS Seven of ten case-control studies were neovascular AMD, and few studies came from west and north of China. There was strong evidence for association between CFH and AMD in Chinese population, with those having risk allele C 2.35 times more likely to have AMD than subjects with T allele. Evidence of publication bias was not observed in our meta-analysis. CONCLUTION This meta-analysis summarizes the strong evidence for an association between CFH and AMD in Chinese and indicates each C allele increasing the odds of AMD by 2.33-fold.But more evidences about the relation between CFH polymorphism and different type of Chinese AMD from various district were needed. PMID:22762059

  14. C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration (AMD)

    PubMed Central

    Bhutto, Imran A; Baba, Takayuki; Merges, Carol; Juriasinghani, Vikash; McLeod, D Scott; Lutty, Gerard A

    2016-01-01

    Background There is increasing evidence that inflammation and immune-mediated processes (complement activation) play an important role in age-related macular degeneration (AMD) pathogenesis. A genetic variation in the complement factor H (CFH) gene and plasma levels of C-reactive protein (CRP), a systemic marker of subclinical inflammation, have been consistently shown to be associated with an increased risk for AMD. In the present study, we examined the immunolocalization of CRP and CFH in aged control human donor eyes (n=10; mean age 79 yrs) and eyes with AMD (n=18; mean age 83 yrs). Methods Alkaline phosphatase immunohistochemistry was performed using polyclonal antibodies against CRP and CFH on cryopreserved tissue sections from disc/macular blocks. Three independent masked observers scored the reaction product (0-8). Results In aged control eyes, the retinal pigment epithelium/Bruch’s membrane/choriocapillaris (RPE/BrM/CC) complex including intercapillary septa (ICS) had the most prominent immunostaining for CRP and CFH. CRP was significantly higher than controls in BrM/CC/ICS and choroidal stroma in early and wet AMD eyes (p<0.05). In contrast, CFH was significantly lower in BrM/CC/ICS complex of AMD choroids than in controls (p<0.05). Interestingly, CRP and CFH were significantly reduced in BrM/CC/ICS complex in atrophic area of macula in geographic atrophy (GA)(p<0.05). Drusen and basal laminar deposits were intensely positive for CRP and CFH. Conclusion These immunohistochemical findings show that changes in distribution and relative levels of CRP and CFH were evident in early and late AMD eyes. This suggests that high levels of CRP and insufficient CFH at the retina/choroid interface may lead to uncontrolled complement activation with associated cell and tissue damage. This study supports the hypothesis that inflammation and immune-mediated mechanisms are involved in the pathogenesis of AMD. PMID:21633121

  15. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy. PMID:25715554

  16. APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy Study.

    PubMed

    Hoy, Wendy E; Hughson, Michael D; Kopp, Jeffrey B; Mott, Susan A; Bertram, John F; Winkler, Cheryl A

    2015-12-01

    APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom) and mean glomerular volume (V glom) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥ 30 kg/m(2), enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans. PMID:26038529

  17. Growth differentiation factor 6 derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues

    PubMed Central

    Hisamatsu, Daisuke; Ohno-Oishi, Michiko; Nakamura, Shiho; Mabuchi, Yo; Naka-Kaneda, Hayato

    2016-01-01

    The senescence-associated secretory phenotype (SASP) has attracted attention as a mechanism that connects cellular senescence to tissue dysfunction, and specific SASP factors have been identified as systemic pro-aging factors. However, little is known about the age-dependent changes in the secretory properties of stem cells. Young, but not old, mesenchymal stem/stromal cells (MSCs) are a well-known source of critical regenerative factors, but the identity of these factors remains elusive. In this study, we identified growth differentiation factor 6 (Gdf6; also known as Bmp13 and CDMP-2) as a regenerative factor secreted from young MSCs. The expression of specific secretory factors, including Gdf6, was regulated by the microRNA (miRNA) miR-17, whose expression declined with age. Upregulation of Gdf6 restored the osteogenic capacity of old MSCs in vitro and exerted positive effects in vivo on aging-associated pathologies such as reduced lymphopoiesis, insufficient muscle repair, reduced numbers of neural progenitors in the brain, and chronic inflammation. Our results suggest that manipulation of miRNA could enable control of the SASP, and that regenerative factors derived from certain types of young cells could be used to treat geriatric diseases. PMID:27311402

  18. Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project

    PubMed Central

    Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L.

    2011-01-01

    This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21–30, 31–40, 41–50, 51–60, 61–70, and 71–80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes. PMID:22187622

  19. Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project.

    PubMed

    Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L

    2011-01-01

    This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes. PMID:22187622

  20. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

    PubMed Central

    Bhutto, Imran A.; McLeod, D. Scott; Hasegawa, Takuya; Kim, Sahng Y.; Merges, Carol; Tong, Patrick; Lutty, Gerard A.

    2016-01-01

    The purpose of this study was to examine the localization and relative levels of vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid and to determine if the localization or their relative levels changed in age-related macular degeneration (AMD). Ocular tissues were obtained from eight aged control donors (age range, 75–86 years; mean age, 79.8 years) with no evidence or history of chorioretinal disease and from 12 donors diagnosed with AMD (age range, 61–105 years; mean age, 83.9 years). Tissues were cryopreserved and streptavidin alkaline phosphatase immunohistochemistry was performed with rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF antibodies. Binding of the antibodies was blocked by preincubation of the antibody with an excess of recombinant human PEDF or VEGF peptide. Choroidal blood vessels were identified with mouse anti-human CD-34 antibody in adjacent tissue sections. Three independent observers graded the immunohistochemical reaction product. The most prominent sites of VEGF and PEDF localization in aged control choroid were RPE–Bruch’s membrane–choriocapillaris complex including RPE basal lamina, intercapillary septa, and choroidal stroma. There was no significant difference in immunostaining intensity and localization of VEGF and PEDF in aged control choroids. The most intense VEGF immunoreactivity was observed in leukocytes within blood vessels. AMD choroid had a similar pattern and intensity of VEGF immunostaining to that observed in aged controls. However, PEDF immunoreactivity was significantly lower in RPE cells (p = 0.0073), RPE basal lamina (p = 0.0141), Bruch’s membrane (p < 0.0001), and choroidal stroma (p = 0.0161) of AMD choroids. The most intense PEDF immunoreactivity was observed in disciform scars. Drusen and basal laminar deposits (BLDs) were positive for VEGF and PEDF. In aged control subjects

  1. Nonsynonymous single nucleotide polymorphisms in the complement component 3 gene are associated with risk of age-related macular degeneration: a meta-analysis.

    PubMed

    Qian-Qian, Yu; Yong, Yao; Jing, Zhu; Xin, Bao; Tian-Hua, Xie; Chao, Sun; Jia, Cao

    2015-05-01

    Nonsynonymous single nucleotide polymorphisms (SNPs) in complement component 3 (CC3) are associated with the risk of age-related macular degeneration (AMD), however, this association is not consistent among studies. To thoroughly address this issue, we performed an updated meta-analysis to evaluate the association between nine SNPs in the CC3 gene and AMD risk. A search was conducted of the PubMed database through 3rd Aug, 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of associations. Based on the search criteria for manuscripts reporting AMD susceptibility related to CC3 in nine SNPs, 57 case-control studies from 22 different articles were retrieved. Significantly positive associations were found for the rs2230199 C/G SNP and AMD in the Caucasian population, as well as for the rs1047286 C/T SNP. Moreover, a relationship between the rs11569536 G/A SNP and AMD was detected. By contrast, a negative association was observed between rs2250656 A/G SNP and AMD risk. The present meta-analysis suggests that these four SNPs in the CC3 gene are potentially associated with the risk of AMD development. Further studies using larger sample sizes and accounting for gene-environment interactions should be conducted to elucidate the role of CC3 gene polymorphisms in AMD risk. PMID:25688879

  2. Emerging roles of frailty and inflammaging in risk assessment of age-related chronic diseases in older adults: the intersection between aging biology and personalized medicine.

    PubMed

    Wu, I-Chien; Lin, Cheng-Chieh; Hsiung, Chao A

    2015-01-01

    A chronic disease in older adults usually runs a course that is less predictable than in younger individuals. Unexplained variations in disease incidence, prognosis, therapeutic responses, and toxicity are frequently observed among older adults. This heterogeneity poses huge challenges to the current one-size-fits-all health care systems, and calls for more personalized managements of chronic diseases in older adults. Aging is characterized by progressive deterioration of bodily functions with increasing risk of failure over time. The entire process is hierarchically organized, and progresses from intracellular events to changes at systemic and ultimately organism levels at different rates among different individuals. Aging biology exerts great influences on the development and progression of most age-related chronic diseases. Thus, aging biology could contribute to the complexity of illnesses that increase with age, and aging biomarkers possess a great potential to enable personalized health risk assessment and health care. We review evidences supporting the roles of aging biomarkers in risk assessment of prevalent age-related diseases. Frailty phenotype is an objectively measured indicator of advanced-stage aging that is characterized by organism-level dysfunction. In contrast, altered inflammation markers level signifies an earlier stage between cellular abnormalities and systems dysfunction. Results of human observational studies and randomized controlled trials indicate that these measures, albeit simple, greatly facilitate classification of older patients with cancer, chronic kidney disease, cardiovascular diseases and type 2 diabetes mellitus into groups that vary in disease incidence, prognosis and therapeutic response/toxicity. As the detailed mechanisms underlying the complex biologic process of aging are unraveled in the future, a larger array of biomarkers that correlate with biologic aging at different stages will be discovered. Following the

  3. Omega-3 Supplementation Combined With Anti–Vascular Endothelial Growth Factor Lowers Vitreal Levels of Vascular Endothelial Growth Factor in Wet Age-Related Macular Degeneration

    PubMed Central

    REZENDE, FLAVIO A.; LAPALME, ERIC; QIAN, CYNTHIA X.; SMITH, LOIS E.; SANGIOVANNI, JOHN PAUL; SAPIEHA, PRZEMYSLAW

    2015-01-01

    PURPOSE To determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment. DESIGN Prospective, randomized, open-label, single-center, clinical trial, consecutive interventional case series. METHODS The study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n = 10) or without omega-3 fatty acids (group 2, n = 10). They were compared with an anti-VEGF treatment-naïve wet AMD group (group 3, n = 10) and an epiretinal membrane or macular hole group (group 4, n = 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3 months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively. RESULTS Patients receiving omega-3s (group 1) had significantly lower levels of vitreal VEGF-A (141.11 ± 61.89 pg/mL) when compared with group 2 (626.09 ± 279.27 pg/mL; P = .036) and group 3 (735.48 ± 216.43 pg/mL; P = .013), but similar levels to group 4 (235.81 ± 33.99 pg/mL; P=.215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements. CONCLUSIONS This study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients. PMID:25089351

  4. Development and Validation of an Older Occupant Finite Element Model of a Mid-Sized Male for Investigation of Age-related Injury Risk.

    PubMed

    Schoell, Samantha L; Weaver, Ashley A; Urban, Jillian E; Jones, Derek A; Stitzel, Joel D; Hwang, Eunjoo; Reed, Matthew P; Rupp, Jonathan D; Hu, Jingwen

    2015-11-01

    The aging population is a growing concern as the increased fragility and frailty of the elderly results in an elevated incidence of injury as well as an increased risk of mortality and morbidity. To assess elderly injury risk, age-specific computational models can be developed to directly calculate biomechanical metrics for injury. The first objective was to develop an older occupant Global Human Body Models Consortium (GHBMC) average male model (M50) representative of a 65 year old (YO) and to perform regional validation tests to investigate predicted fractures and injury severity with age. Development of the GHBMC M50 65 YO model involved implementing geometric, cortical thickness, and material property changes with age. Regional validation tests included a chest impact, a lateral impact, a shoulder impact, a thoracoabdominal impact, an abdominal bar impact, a pelvic impact, and a lateral sled test. The second objective was to investigate age-related injury risks by performing a frontal US NCAP simulation test with the GHBMC M50 65 YO and the GHBMC M50 v4.2 models. Simulation results were compared to the GHBMC M50 v4.2 to evaluate the effect of age on occupant response and risk for head injury, neck injury, thoracic injury, and lower extremity injury. Overall, the GHBMC M50 65 YO model predicted higher probabilities of AIS 3+ injury for the head and thorax. PMID:26660751

  5. Age-Related Yield of Adipose-Derived Stem Cells Bearing the Low-Affinity Nerve Growth Factor Receptor

    PubMed Central

    González-Garza, Maria Teresa; Cardenas-Lopez, Alejandro; Chavez-Castilla, Luis; Cruz-Vega, Delia Elva; Moreno-Cuevas, Jorge E.

    2013-01-01

    Adipose-derived stem cells (ADSCs) are a heterogeneous cell population that may be enriched by positive selection with antibodies against the low-affinity nerve growth factor receptor (LNGFR or CD271), yielding a selective cell universe with higher proliferation and differentiation potential. This paper addresses the need for determining the quantity of ADSCs positive for the CD271 receptor and its correlation with donor's age. Mononuclear cells were harvested from the lower backs of 35 female donors and purified using magnetic beads. Multipotency capacity was tested by the expression of stemness genes and through differentiation into preosteoblasts and adipocytes. A significant statistical difference was found in CD271+ concentrations between defined age intervals. The highest yield was found within women on the 30–40-year-old age range. CD271+ ADSCs from all age groups showed differentiation capabilities as well as expression of typical multipotent stem cell genes. Our data suggest that the amount of CD271+ cells correlates inversely with age. However, the ability to obtain these cells was maintained through all age ranges with a yield higher than what has been reported from bone marrow. Our findings propose CD271+ ADSCs as the primary choice for tissue regeneration and autologous stem cell therapies in older subjects. PMID:24376462

  6. Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.

    PubMed

    Ilia, Maria; Sugiyama, Yuka; Price, Jack

    2003-06-26

    Oct-6 is a POU III domain transcription factor whose primary role is thought to be developmental. It is expressed in embryonic stem cells, Schwann cells, and in neuronal subpopulations during telencephalic development. Its best characterised role is in Schwann cells where it is thought to regulate myelin specific gene expression. Expression of Oct-6 was recently discovered in neurons in post-mortem human schizophrenic specimens while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain, and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression via in situ hybridisation and Western blot analysis in normal adult female mice of different ages. We show that both RNA and protein levels of Oct-6 expression are highly sustained in the adult and aging cerebellum, whereas they are attenuated in the telencephalon by PW30 (postnatal week 30). These observations suggest that Oct-6 expression takes place in a sex and age dependent way. PMID:12782346

  7. A Comparative Study of Age-Related Hearing Loss in Wild Type and Insulin-Like Growth Factor I Deficient Mice

    PubMed Central

    Riquelme, Raquel; Cediel, Rafael; Contreras, Julio; Lourdes, Rodriguez-de la Rosa; Murillo-Cuesta, Silvia; Hernandez-Sanchez, Catalina; Zubeldia, Jose M.; Cerdan, Sebastian; Varela-Nieto, Isabel

    2010-01-01

    Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or

  8. Smoking and Age-Related Macular Degeneration: Review and Update

    PubMed Central

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  9. Age-related eye disease and gender.

    PubMed

    Zetterberg, Madeleine

    2016-01-01

    Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease. PMID:26508081

  10. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  11. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  12. Factors in risk perception

    PubMed

    Sjoberg

    2000-02-01

    Risk perception is a phenomenon in search of an explanation. Several approaches are discussed in this paper. Technical risk estimates are sometimes a potent factor in accounting for perceived risk, but in many important applications it is not. Heuristics and biases, mainly availability, account for only a minor portion of risk perception, and media contents have not been clearly implicated in risk perception. The psychometric model is probably the leading contender in the field, but its explanatory value is only around 20% of the variance of raw data. Adding a factor of "unnatural risk" considerably improves the psychometric model. Cultural Theory, on the other hand, has not been able to explain more than 5-10% of the variance of perceived risk, and other value scales have similarly failed. A model is proposed in which attitude, risk sensitivity, and specific fear are used as explanatory variables; this model seems to explain well over 30-40% of the variance and is thus more promising than previous approaches. The model offers a different type of psychological explanation of risk perception, and it has many implications, e.g., a different approach to the relationship between attitude and perceived risk, as compared with the usual cognitive analysis of attitude. PMID:10795334

  13. Pro-Insulin-Like Growth Factor-II Ameliorates Age-Related Inefficient Regenerative Response by Orchestrating Self-Reinforcement Mechanism of Muscle Regeneration.

    PubMed

    Ikemoto-Uezumi, Madoka; Uezumi, Akiyoshi; Tsuchida, Kunihiro; Fukada, So-ichiro; Yamamoto, Hiroshi; Yamamoto, Naoki; Shiomi, Kosuke; Hashimoto, Naohiro

    2015-08-01

    Sarcopenia, age-related muscle weakness, increases the frequency of falls and fractures in elderly people, which can trigger severe muscle injury. Rapid and successful recovery from muscle injury is essential not to cause further frailty and loss of independence. In fact, we showed insufficient muscle regeneration in aged mice. Although the number of satellite cells, muscle stem cells, decreases with age, the remaining satellite cells maintain the myogenic capacity equivalent to young mice. Transplantation of young green fluorescent protein (GFP)-Tg mice-derived satellite cells into young and aged mice revealed that age-related deterioration of the muscle environment contributes to the decline in regenerative capacity of satellite cells. Thus, extrinsic changes rather than intrinsic changes in satellite cells appear to be a major determinant of inefficient muscle regeneration with age. Comprehensive protein expression analysis identified a decrease in insulin-like growth factor-II (IGF-II) level in regenerating muscle of aged mice. We found that pro- and big-IGF-II but not mature IGF-II specifically express during muscle regeneration and the expressions are not only delayed but also decreased in absolute quantity with age. Supplementation of pro-IGF-II in aged mice ameliorated the inefficient regenerative response by promoting proliferation of satellite cells, angiogenesis, and suppressing adipogenic differentiation of platelet derived growth factor receptor (PDGFR)α(+) mesenchymal progenitors. We further revealed that pro-IGF-II but not mature IGF-II specifically inhibits the pathological adipogenesis of PDGFRα(+) cells. Together, these results uncovered a distinctive pro-IGF-II-mediated self-reinforcement mechanism of muscle regeneration and suggest that supplementation of pro-IGF-II could be one of the most effective therapeutic approaches for muscle injury in elderly people. PMID:25917344

  14. Genetic and Environmental Underpinnings to Age-Related Ocular Diseases

    PubMed Central

    Seddon, Johanna M.

    2013-01-01

    Age-related macular degeneration (AMD), cataract, glaucoma and diabetic retinopathy are common causes of visual loss. Both environmental and genetic factors contribute to the development of these diseases. The modifiable factors related to some of these age-related and visually threatening diseases are smoking, obesity, and dietary factors, and a cardiovascular risk profile. Many common and a few rare genetic factors are associated with AMD. The role of genetic variants for the other diseases are less clear. Interactions between environmental, therapeutic, and genetic factors are being explored. Knowledge of genetic risk and environmental factors, especially for AMD, has grown markedly over the past 2.5 decades and has led to some sight-saving approaches in preventive management. PMID:24335064

  15. Sex Differences in Age-Related Decline of Urinary Insulin-Like Growth Factor-Binding Protein-3 Levels in Adult Bonobos and Chimpanzees.

    PubMed

    Behringer, Verena; Wudy, Stefan A; Blum, Werner F; Stevens, Jeroen M G; Remer, Thomas; Boesch, Christophe; Hohmann, Gottfried

    2016-01-01

    There is increasing interest in the characterization of normative senescence in humans. To assess to what extent aging patterns in humans are unique, comparative data from closely related species, such as non-human primates, can be very useful. Here, we use data from bonobos and chimpanzees, two closely related species that share a common ancestor with humans, to explore physiological markers that are indicative of aging processes. Many studies on aging in humans focus on the somatotropic axis, consisting of growth hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins (IGFBPs). In humans, IGFBP-3 levels decline steadily with increasing age. We used urinary IGFBP-3 levels as an alternative endocrine marker for IGF-I to identify the temporal pattern known to be related with age-related changes in cell proliferation, growth, and apoptosis. We measured urinary IGFBP-3 levels in samples from 71 bonobos and 102 chimpanzees. Focusing on samples from individuals aged 10 years or older, we found that urinary IGFBP-3 levels decline in both ape species with increasing age. However, in both species, females start with higher urinary IGFBP-3 levels than males, experience a steeper decline with increasing age, and converge with male levels around the age of 30-35 years. Our measurements of urinary IGFBP-3 levels indicate that bonobos and chimpanzees mirror human patterns of age-related decline in IGFBP-3 in older individuals (<10 years) of both sexes. Moreover, such as humans, both ape species show sex-specific differences in IGFBP-3 levels with females having higher levels than males, a result that correlates with sex differences in life expectancy. Using changes in urinary IGFBP-3 levels as a proxy for changes in GH and IGF-I levels that mark age-related changes in cell proliferation, this approach provides an opportunity to investigate trade-offs in life-history strategies in cross-sectional and in longitudinal studies, both in captivity and in the

  16. Sex Differences in Age-Related Decline of Urinary Insulin-Like Growth Factor-Binding Protein-3 Levels in Adult Bonobos and Chimpanzees

    PubMed Central

    Behringer, Verena; Wudy, Stefan A.; Blum, Werner F.; Stevens, Jeroen M. G.; Remer, Thomas; Boesch, Christophe; Hohmann, Gottfried

    2016-01-01

    There is increasing interest in the characterization of normative senescence in humans. To assess to what extent aging patterns in humans are unique, comparative data from closely related species, such as non-human primates, can be very useful. Here, we use data from bonobos and chimpanzees, two closely related species that share a common ancestor with humans, to explore physiological markers that are indicative of aging processes. Many studies on aging in humans focus on the somatotropic axis, consisting of growth hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins (IGFBPs). In humans, IGFBP-3 levels decline steadily with increasing age. We used urinary IGFBP-3 levels as an alternative endocrine marker for IGF-I to identify the temporal pattern known to be related with age-related changes in cell proliferation, growth, and apoptosis. We measured urinary IGFBP-3 levels in samples from 71 bonobos and 102 chimpanzees. Focusing on samples from individuals aged 10 years or older, we found that urinary IGFBP-3 levels decline in both ape species with increasing age. However, in both species, females start with higher urinary IGFBP-3 levels than males, experience a steeper decline with increasing age, and converge with male levels around the age of 30–35 years. Our measurements of urinary IGFBP-3 levels indicate that bonobos and chimpanzees mirror human patterns of age-related decline in IGFBP-3 in older individuals (<10 years) of both sexes. Moreover, such as humans, both ape species show sex-specific differences in IGFBP-3 levels with females having higher levels than males, a result that correlates with sex differences in life expectancy. Using changes in urinary IGFBP-3 levels as a proxy for changes in GH and IGF-I levels that mark age-related changes in cell proliferation, this approach provides an opportunity to investigate trade-offs in life-history strategies in cross-sectional and in longitudinal studies, both in captivity and in

  17. Risk Factors for Tuberculosis

    PubMed Central

    Narasimhan, Padmanesan; Wood, James; MacIntyre, Chandini Raina; Mathai, Dilip

    2013-01-01

    The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV), malnutrition, and young age), emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli. PMID:23476764

  18. Clinical Outcomes of Eyes with Submacular Hemorrhage Secondary to Age-related Macular Degeneration Treated with Anti-vascular Endothelial Growth Factor

    PubMed Central

    Kim, Kun Hae; Chang, Young Suk; Lee, Tae Gon; Kim, Jong Woo; Lew, Young Ju

    2015-01-01

    Purpose To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy for patients diagnosed with submacular hemorrhage secondary to exudative age-related macular degeneration. Methods This retrospective, observational study included 49 patients (49 eyes) who initially presented with submacular hemorrhage associated with exudative age-related macular degeneration and who were followed-up for at least 24 months. Only eyes that were treated with intravitreal anti-VEGF monotherapy were included in the study. Best-corrected visual acuity (BCVA) measurements obtained at diagnosis, six months, and the final visit were compared. The associations of BCVA at the final visit with baseline BCVA, BCVA at six months, symptom duration, hemorrhage extent, and central foveal thickness were also analyzed. Results Over the course of follow-up (mean, 32.1 ± 8.5 months), an average of 5.1 ± 2.2 anti-VEGF injections were administered. Recurrent hemorrhage was noted in 13 eyes (26.5%). The mean logarithm of the minimal angle of resolution BCVA at diagnosis, six months, and the final visit were 1.40 ± 0.52, 0.87 ± 0.64, and 1.03 ± 0.83, respectively. Both baseline BCVA (p = 0.012) and BCVA at six months (p < 0.001) were significantly associated with BCVA at the final visit. Conclusions Improved visual acuity was maintained for more than two years with intravitreal anti-VEGF monotherapy. BCVA at six months is a useful clinical index to predict long-term visual prognosis. PMID:26457037

  19. Is age-related failure of metabolic reprogramming a principal mediator in idiopathic Parkinson's disease? Implications for treatment and inverse cancer risk.

    PubMed

    Engel, Peter A

    2016-08-01

    Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder characterized by selective degeneration of the substantia nigra pars compacta (SNc), dorsal motor nucleus of the vagus and other vulnerable nervous system regions characterized by extensive axonal arborization and intense energy requirements. Systemic age-related depression of mitochondrial function, oxidative phosphorylation (OXPHOS) and depressed expression of genes supporting energy homeostasis is more severe in IPD than normal aging such that energy supply may exceed regional demand. In IPD, the overall risk of malignancy is reduced. Cancer is a collection of proliferative diseases marked by malignant transformation, dysregulated mitosis, invasion and metastasis. Many cancers demonstrate normal mitochondrial function, preserved OXPHOS, competent mechanisms of energy homeostasis, and metabolic reprogramming capacities that are lacking in IPD. Metabolic reprogramming adjusts OXPHOS and glycolytic pathways in response to changing metabolic needs. These opposite metabolic features form the basis of a two component hypothesis. First, that depressed mitochondrial function, OXPHOS deficiency and impaired metabolic reprogramming contribute to focal energy failure, neurodegeneration and disease expression in IPD. Second, that the same systemic metabolic deficits inhibit development and proliferation of malignancies in IPD. Studies of mitochondrial aging, familial PD (FPD), the lysosomal storage disorder, Gaucher's disease, Parkinson's disease cybrids, the mitochondrial cytopathies, and disease-related metabolic reprogramming both in IPD and cancer provide support for this model. PMID:27372878

  20. Age-related decreases of serum-response factor levels in human mesenchymal stem cells are involved in skeletal muscle differentiation and engraftment capacity.

    PubMed

    Ting, Chiao-Hsuan; Ho, Pai-Jiun; Yen, Betty Linju

    2014-06-01

    Skeletal muscle (SkM) comprise ∼40% of human body weight. Injury or damage to this important tissue can result in physical disability, and in severe cases is difficult for its endogenous stem cell-the satellite cell-to reverse effectively. Mesenchymal stem cells (MSC) are postnatal progenitor/stem cells that possess multilineage mesodermal differentiation capacity, including toward SkM. Adult bone marrow (BM) is the best-studied source of MSCs; however, aging also decreases BMMSC numbers and can adversely affect differentiation capacity. Therefore, we asked whether human sources of developmentally early stage mesenchymal stem cells (hDE-MSCs) isolated from embryonic stem cells, fetal bone, and term placenta could be cellular sources for SkM repair. Under standard muscle-inducing conditions, hDE-MPCs differentiate toward a SkM lineage rather than cardiomyocytic or smooth muscle lineages, as evidenced by increased expression of SkM-associated markers and in vitro myotube formation. In vivo transplantation revealed that SkM-differentiated hDE-MSCs can efficiently incorporate into host SkM tissue in a mouse model of SkM injury. In contrast, adult BMMSCs do not express SkM-associated genes after in vitro SkM differentiation nor engraft in vivo. Further investigation of possible factors responsible for this difference in SkM differentiation potential revealed that, compared with adult BMMSCs, hDE-MSCs expressed higher levels of serum response factor (SRF), a transcription factor critical for SkM lineage commitment. Moreover, knockdown of SRF in hDE-MSCs resulted in decreased expression of SkM-related genes after in vitro differentiation and decreased in vivo engraftment. Our results implicate SRF as a key factor in age-related SkM differentiation capacity of MSCs, and demonstrate that hDE-MSCs are possible candidates for SkM repair. PMID:24576136

  1. Thyroid Cancer Risk Factors

    MedlinePlus

    ... and radiation fallout from power plant accidents or nuclear weapons. Having had head or neck radiation treatments in childhood is a risk factor for ... should be done using the lowest dose of radiation that still provides a clear ... from nuclear weapons or power plant accidents. For instance, thyroid ...

  2. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  3. Perioperative allergy: risk factors.

    PubMed

    Caffarelli, C; Stringari, G; Pajno, G B; Peroni, D G; Franceschini, F; Dello Iacono, I; Bernardini, R

    2011-01-01

    Perioperative anaphylactic as well as anaphylactoid reactions can be elicited by drugs, diagnostic agents, antiseptics, disinfectants and latex. In some individuals, allergic reactions occur in the absence of any evident risk factor. Previous history of specific safe exposure to a product does not permit to exclude the risk of having a reaction. We have systematically reviewed characteristics in the patient's history or clinical parameters that affect the risk of developing reactions during anesthesia. Evidence shows that patients with previous unexplained reaction during anesthesia are at risk for perioperative allergic reactions. An allergic reaction to an agent is associated with previous reaction to a product that is related with the culprit agent. Multiple surgery procedures, professional exposure to latex and allergy to fruit are associated with an increased frequency of latex allergy. It has been shown that in some instances, allergic perioperative reactions may be more common in atopic patients and in females. PMID:22014923

  4. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review.

    PubMed

    Lanzetta, Paolo; Mitchell, Paul; Wolf, Sebastian; Veritti, Daniele

    2013-12-01

    Antivascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of wet age-related macular degeneration (wAMD). Recent research has focused on evaluating competing agents and alternative dosage regimens, providing evidence to help determine optimal treatment strategies. We therefore conducted a review of clinical research studies in wAMD published since 2008 that compared anti-VEGF dosing regimens and therapies; seven studies met our inclusion criteria. Data on baseline disease characteristics, disease outcomes, safety (ocular and systemic) and treatment burden (injection and visit frequencies) were extracted on patients treated with ranibizumab 0.5 mg, bevacizumab 1.25 mg or aflibercept 2.0 mg for up to 2 years. For ranibizumab and bevacizumab, visual and anatomical outcomes at 1 and 2 years were superior using scheduled monthly (or 4 weekly (q4w)) compared with as needed or scheduled quarterly dosing regimens. Treatment outcomes were generally better for both drugs when more aggressive retreatment criteria were used, which resulted in more frequent injections. Bevacizumab, however, was associated with a 30-35% elevated rate of serious systemic adverse events compared with ranibizumab, regardless of dosing interval; further study in larger patient populations will be required to determine the validity of this finding. Intravitreal aflibercept injection every 8 weeks was non-inferior to ranibizumab q4w on all visual and anatomical endpoints at week 52, had a similar safety profile and required five fewer anti-VEGF injections. PMID:23929309

  5. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration.

    PubMed

    Mrejen, Sarah; Jung, Jesse J; Chen, Christine; Patel, Samir N; Gallego-Pinazo, Roberto; Yannuzzi, Nicolas; Xu, Luna; Marsiglia, Marcela; Boddu, Sucharita; Freund, K Bailey

    2015-01-01

    With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1-6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4-13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes. PMID:26239682

  6. Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration.

    PubMed

    Koenig, Patrick; Lee, Chingwei V; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F; Fuh, Germaine

    2015-09-01

    The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. PMID:26088137

  7. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. PMID:26292978

  8. Risk Factors in Stroke

    PubMed Central

    Mustacchi, Piero

    1985-01-01

    In the United States, stroke accounts for 160,000 annual deaths; only 16% of the 1.8 million stroke survivors are fully independent. The incidence of stroke increases with age. Hemorrhagic strokes outnumber ischemic strokes before age 15. Japanese men in this country have a lower stroke mortality than their age peers in Japan. Excessive stroke mortality for US nonwhites may not be entirely due to the greater prevalence of hypertension among blacks. Hypertension emerges as the single most powerful and reversible risk factor in stroke and for survival after stroke. Impaired cardiac function is the second most important precursor of stroke. The recurrence of stroke in survivors is high. The frequency of completed stroke is high in persons with transient ischemic attacks, but not in those with asymptomatic carotid bruits. Other reversible risk factors are smoking, the use of oral contraceptives, alcoholic excess, a low level of physical activity, blood hyperviscosity and drug abuse. PMID:3898597

  9. Breast cancer risk factors

    PubMed Central

    Ciszewski, Tomasz; Łopacka-Szatan, Karolina; Miotła, Paweł; Starosławska, Elżbieta

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence. PMID:26528110

  10. Bruch's membrane diffusivity for vascular endothelial growth factors may explain variable response to wet age-related macular degeneration treatment: clinical implications.

    PubMed

    Peddada, Ram R

    2014-12-01

    The hypothesis presented is that diffusivity of vascular endothelial growth factors (VEGF) across Bruch's membrane is an important parameter that distinguishes prompt and slow responders to anti-VEGF treatment in wet age-related macular degeneration (AMD). Accordingly, slow-responders have a high diffusivity and will attain peak VEGF levels on the choroidal side of Bruch's membrane rapidly, probably before or around the time of the next monthly anti-VEGF injection. If a fixed dose of anti-VEGF is used at each monthly treatment (as is the current practice), depending on the initial level of VEGF at that time of injection, VEGF with each treatment will vary. Therefore, diffusion will occur at a different concentration gradient in each treatment cycle subsequent to the injection. Hence, by Fick's Second Law of Diffusion, the slope of the concentration versus time curve for each treatment cycle will be different from the preceding cycle. This leads to a different peak concentration just prior to the next monthly injection. So, when a fixed dose of the anti-VEGF is used at each monthly treatment peak VEGF level fluctuates instead of going down continuously which prolongs the treatment. Thus, doses of anti-VEGF may have to be tapered to decrease the concentration gradient and to slow down the rate of diffusion of VEGF. Diffusivity of Bruch's membrane with regards to VEGF is a simple concept that can explain the variable response to anti-VEGF treatment in wet AMD. If validated through clinical trial the treatment protocol for wet AMD can be more precise and tailored to individual patients. PMID:25468789

  11. Delay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration

    PubMed Central

    LIM, JONATHAN H.; WICKREMASINGHE, SANJEEWA S.; XIE, JING; CHAUHAN, DEVINDER S.; BAIRD, PAUL N.; ROBMAN, LUBA D.; HAGEMAN, GREGORY; GUYMER, ROBYN H.

    2016-01-01

    PURPOSE To investigate the potential influences that affect visual acuity (VA) outcome in a clinic-based cohort of age-related macular degeneration (AMD) patients undergoing anti–vascular endothelial growth factor (anti-VEGF) treatment for choroidal neovascularization. DESIGN Prospective interventional case series. METHODS Patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were prospectively recruited. A detailed questionnaire was given to patients at time of enrollment, to collect information relating to demographics, history of visual symptoms, visual acuity (VA), and treatment scheduling. Delay from symptoms to treatment (“Treatment delay”) was measured in terms of weeks and analyzed in tertiles. Information pertaining to treatment outcomes was collected over a 6-month period. RESULTS One hundred eighty-five eyes of 185 patients were recruited into the study. Longer delay from first symptoms suggestive of CNV to first injection was a significant predictor (P = .015) of poorer treatment outcome, when controlling for age, sex, and baseline VA. Patients with a delay in treatment of 21 weeks or more compared to a delay of 7 weeks or less had an odds ratio of 2.62 (1.20, 5.68) for worsening vision after treatment. CONCLUSIONS Patients experiencing a longer delay between their first symptoms of CNV and their first anti-VEGF treatment have a significantly lower chance of improving vision at 6 months following anti-VEGF therapy. It is critical that this information reach those at potential vision loss from AMD, in order that prompt treatment may be instituted, to maximize the benefits of anti-VEGF treatment. PMID:22245460

  12. Review: Axon pathology in age-related neurodegenerative disorders.

    PubMed

    Adalbert, R; Coleman, M P

    2013-02-01

    'Dying back' axon degeneration is a prominent feature of many age-related neurodegenerative disorders and is widespread in normal ageing. Although the mechanisms of disease- and age-related losses may differ, both contribute to symptoms. Here, we review recent advances in understanding axon pathology in age-related neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and glaucoma. In particular, we highlight the importance of axonal transport, autophagy, traumatic brain injury and mitochondrial quality control. We then place these disease mechanisms in the context of changes to axons and dendrites that occur during normal ageing. We discuss what makes ageing such an important risk factor for many neurodegenerative disorders and conclude that the processes of normal ageing and disease combine at the molecular, cellular or systems levels in a range of disorders to produce symptoms. Pathology identical to disease also occurs at the cellular level in most elderly individuals. Thus, normal ageing and age-related disease are inextricably linked and the term 'healthy ageing' downplays the important contributions of cellular pathology. For a full understanding of normal ageing or age-related disease we must study both processes. PMID:23046254

  13. Risk Factors for Eating Disorders

    ERIC Educational Resources Information Center

    Striegel-Moore, Ruth H.; Bulik, Cynthia M.

    2007-01-01

    The authors review research on risk factors for eating disorders, restricting their focus to studies in which clear precedence of the hypothesized risk factor over onset of the disorder is established. They illustrate how studies of sociocultural risk factors and biological factors have progressed on parallel tracks and propose that major advances…

  14. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity. PMID:25156204

  15. Association of gene polymorphism with serum levels of inflammatory and angiogenic factors in Pakistani patients with age-related macular degeneration

    PubMed Central

    Ambreen, Fareeha; Ismail, Muhammad

    2015-01-01

    Purpose To study the association of serum levels of inflammatory mediators and angiogenic factors with genetic polymorphism in Pakistani age-related macular degeneration (AMD) patients. Methods This was a cross-sectional and case-control study that included 90 AMD patients diagnosed through slit-lamp examination, fundoscopy, and ocular coherence tomography. For reference and comparison purposes, 100 healthy age-matched subjects (controls) were also recruited. IL-6, IL-8, VEGF, and CRP levels were estimated in the serum samples of patients and control subjects. Using restriction fragment length polymorphism, single nucleotide polymorphisms were studied in IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227543), VEGF (rs3025039, rs699947), and CRP genes (rs1205, rs1130864). Since the data were obtained from a sample population, the Box–Cox transformation algorithm was applied to reduce heterogeneity of error. Multivariate analyses of variance (M-ANOVA) were applied on the transformed data to investigate the association of serum levels of IL-6, IL-8, VEGF, and CRP with AMD. Genotype and allele frequencies were compared through χ2 tests applying Hardy–Weinberg equilibrium. The serum concentrations of IL-6 and IL-8, VEGF, and CRP between homozygotes and heterozygotes were compared through one-way ANOVA. Significance level was p<0.05. Results Compared to control subjects, serum IL-6 (p<0.0001), IL-8 (p<0.0001), VEGF (p<0.0001), and CRP (p<0.0001) levels were significantly elevated in the AMD patients. For rs1800795, patients with the GG genotype showed significantly raised levels of IL-6 compared to those with GC and CC genotypes (p<0.0001). Serum IL-8 levels were significantly higher in patients with the GG genotype compared to the GC and CC genotypes for the single nucleotide polymorphism (SNP) rs2227543 (p<0.002). Similarly, significantly higher VEGF levels were detected for genotype TT for rs3025039 SNP (p<0.038). However, no significant

  16. Risk Factor Assessment Branch (RFAB)

    Cancer.gov

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  17. Neuromuscular contributions to age-related weakness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related physiological change of neuromuscular function is not a linear process and is likely influenced by various biological and behavioral factors (e.g., genetics, nutrition, physical activity level, comorbidities, etc.). These factors contribute to heterogeneity among older adults, which chal...

  18. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  19. Driving and Age-Related Macular Degeneration

    PubMed Central

    Owsley, Cynthia; McGwin, Gerald

    2009-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research. PMID:20046818

  20. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. PMID:26518628

  1. Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution.

    PubMed

    Tan, Jianxin; Wang, Yajun; Zhang, Nannan; Zhu, Xike

    2016-08-01

    Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly. PMID:27189906

  2. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    PubMed

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age-related

  3. Salivary Gland Cancer: Risk Factors

    MedlinePlus

    ... Factors Request Permissions Print to PDF Salivary Gland Cancer: Risk Factors Approved by the Cancer.Net Editorial Board , 08/ ... anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do ...

  4. Pharmacogenetics and age-related macular degeneration.

    PubMed

    Schwartz, Stephen G; Brantley, Milam A

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID:22046503

  5. Age-related macular degeneration: Complement in action.

    PubMed

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD. PMID:26742632

  6. Stroke prevention: modifying risk factors

    PubMed Central

    Romero, José Rafael; Morris, Jane; Pikula, Aleksandra

    2009-01-01

    Risk factor modification remains as the principal aspect of care for stroke prevention. Understanding of risk factors has advanced and several options are now available to treat modifiable risk factors. However, effective treatment remains a challenging task in clinical practice. Prevention begins with awareness of risk factors by patients and clinicians. Risk factor assessment along with overall stroke risk estimation should be part of evaluation of patients with stroke, and used with careful clinical judgment. In this review we discuss the impact of modifiable traditional vascular risk factors on ischemic stroke, interventions for stroke prevention, and evidence for early treatment of risk factors where available as well as areas of research progress. Emphasis should be paid in education of patients, the community and medical personnel. Future research in the field of genetic determinants of vascular risk factors and stroke will increase our understanding of the underlying mechanisms of cerebrovascular disease and likely result in development of new therapies and individualized programs for stroke prevention. PMID:19124428

  7. Risk Factors for Teenage Fatherhood.

    ERIC Educational Resources Information Center

    Thornberry, Terence P.; Smith, Carolyn A.; Howard, Gregory J.

    1997-01-01

    Uses data from the Rochester Youth Development Study of urban youth (N=615) to identify early risk factors for the likelihood of becoming a teen father. Results show that teen fatherhood is related to a variety of risk factors, such as social class, educational performance, precocious sexual activity, and drug use. (RJM)

  8. Risk Factors for Scleroderma

    MedlinePlus

    ... part of a study, please call the Scleroderma Research Foundation at 1-800-441-CURE. Environmental Risk Some ... is both time consuming and expensive. The Scleroderma Research Foundation continues to fund and facilitate the most promising ...

  9. Age-related hearing loss

    MedlinePlus

    ... is no known single cause of age-related hearing loss. Most commonly, it is caused by changes in the inner ear that occur as you grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following ...

  10. Genetics and age-related macular degeneration: a practical review for the clinician

    PubMed Central

    Schwartz, Stephen G; Hampton, Blake M; Kovach, Jaclyn L; Brantley, Milam A

    2016-01-01

    Age-related macular degeneration is a complex disease, with both genetic and environmental risk factors interacting in unknown ways. Currently, 52 gene variants within 34 loci have been significantly associated with age-related macular degeneration. Two well-studied major genes are complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2). There exist several commercially available tests that are proposed to stratify patients into high-risk and low-risk groups, as well as predict response to nutritional supplementation. However, at present, the bulk of the available peer-reviewed evidence suggests that genetic testing is more useful as a research tool than for clinical management of patients. PMID:27445455

  11. Dietary Approaches that Delay Age-Related Diseases

    PubMed Central

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood

  12. Dietary approaches that delay age-related diseases.

    PubMed

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2-15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet-disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood and

  13. [Glaucoma and age-related macular degeneration intricacy].

    PubMed

    Valtot, F

    2008-07-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among the elderly in Western nations. Age is also a well-known and well-evidenced risk factor for glaucoma. With increasing longevity and the rising prevalence of older people around the world, more and more patients will have glaucoma and AMD. Clinical evaluation of these patients still poses problems for clinicians. It is very important to order the right tests at the right time to distinguish glaucomatous defects from those caused by retinal lesions, because appropriate therapy has a beneficial effect on slowing or halting damage. PMID:18957915

  14. Stroke Risk Factors and Symptoms

    MedlinePlus

    ... effective if given quickly. Every minute counts! "Stroke Risk Factors and Symptoms", NINDS. June 1, 2008. Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  15. Hidden Risk Factors for Women

    MedlinePlus

    ... high cholesterol. “Those are the most common risk factors,” according to Steven J. Kittner, M.D., director of the Maryland Stroke Center at the University of Maryland School of Medicine in Baltimore. “But ...

  16. Cardiac risk factors: environmental, sociodemographic, and behavioral cardiovascular risk factors.

    PubMed

    Anthony, David; George, Paul; Eaton, Charles B

    2014-06-01

    Several environmental exposures are associated with increased risk of coronary heart disease (CHD). Exposure to secondhand smoke may increase the risk by as much as 25% to 30%. Exposure to third hand smoke, residual components of tobacco smoke that remain in the environment after a cigarette is extinguished, also appears to increase risk. These residual components can remain in rooms and automobiles for up to 30 years and enter the body through the skin or via inhalation or ingestion. Exposure to particulate matter air pollution from automobile emissions, power plants, and other sources is yet another environmental risk factor for CHD, resulting in tens of thousands of deaths annually in the United States. Exposure to other environmental toxins, particularly bisphenol A and phthalates, also has been linked to CHD. There are sociodemographic risks for CHD, with numerous studies showing that lower socioeconomic status is associated with higher risk. Behavioral risk factors include poor diet, such as frequent consumption of fast food and processed meals; sleep disturbance; and psychological stress, particularly related to marital or work issues. Finally, although high alcohol consumption is associated with increased CHD risk, moderate alcohol consumption (ie, less than 1 to 2 drinks/day), particularly of wine and possibly beer, appears to reduce the risk. PMID:24936715

  17. TLR4 inhibitor attenuates amyloid-β-induced angiogenic and inflammatory factors in ARPE-19 cells: Implications for age-related macular degeneration.

    PubMed

    Chen, Li; Bai, Yujing; Zhao, Min; Jiang, Yanrong

    2016-04-01

    Subretinally-deposited amyloid-β (Aβ) is an important factor in age‑related macular degradation (AMD) often leading to irreversible blindness in the elderly population. The molecular mechanism underlying Aβ deposition during AMD remains unclear. The expression of inflammatory and angiogenic factors was examined by treatment of retinal pigment epithelial (RPE) cells with the oligomeric form of Aβ (OAβ1-42). Changes in the mRNA expression levels of various cytokines was detected by the QuantiGenePlex 6.0 Reagent system, and the protein expression level was determined by western blotting. Culture supernatants were detected using a multiplex cytokine assay and enzyme-linked immunosorbent assays. The in vitro tube formation was evaluated by a Matrigel assay. The present study highlights that OAβ1‑42 activates the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 and phosphorylation nuclear factor-κB signaling pathway in RPE cells. Additionally, it increased the mRNA and protein expression of interleukin (IL)-6, IL-8, IL-33, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiopoietin 2. Furthermore, the TLR4 inhibitor (COBRA) attenuated the expression of inflammatory and angiogenesis factors, particularly IL-6, IL-8, IL-33, bFGF and VEGF. When human umbilical vein endothelial cells (HUVECs) were co-cultured with the COBRA-treated RPE cell culture supernatant the length of the endothelial cell network (measured by calculating tip cell lengths of endothelial cells) was impaired when compared with the HUVECs that were co‑cultured with the cell supernatant exposed to OAβ1‑42. These results suggest that the TLR4-associated pathway may be a potential target for the treatment of AMD. PMID:26936827

  18. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine. PMID:26646495

  19. Intake of zinc and antioxidant micronutrients and early age-related maculopathy lesions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macular degeneration, the end stage of age-related maculopathy (ARM), is the leading cause of legal blindness worldwide, and few modifiable risk factors are known. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to ARM, and carotenoids to antioxidation, ge...

  20. Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Age-Related Interaction in Adult Lifespan

    PubMed Central

    Huang, Chu-Chung; Liu, Mu-En; Kao, Hung-Wen; Chou, Kun-Hsien; Yang, Albert C.; Wang, Ying-Hsiu; Chen, Tong-Ru; Tsai, Shih-Jen; Lin, Ching-Po

    2016-01-01

    Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21–92 years). Through voxel-based morphometry, we found that participants carrying SORL1 allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and SORL1 suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that SORL1 rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan. PMID:26996954

  1. Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors

    SciTech Connect

    Weiner, R.S.; Bortin, M.M.; Gale, R.P.; Gluckman, E.; Kay, H.E.; Kolb, H.J.; Hartz, A.J.; Rimm, A.A.

    1986-02-01

    Data from 932 patients with leukemia who received bone marrow transplants were analyzed to determine factors associated with an increased risk of developing interstitial pneumonitis. Interstitial pneumonitis developed in 268 patients for a 2-year actuarial incidence of 35 +/- 4% (SD) and with a mortality rate of 24%. Six factors were associated with an increased risk: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.3; p less than 0.0002); older age (relative risk, 2.1; p less than 0.0001); presence of severe graft-versus-host disease (relative risk, 1.9; p less than 0.003); long interval from diagnosis to transplantation (relative risk, 1.6; p less than 0.002); performance ratings before transplantation of less than 100% (relative risk, 2.1; p less than 0.0001); and high dose-rates of irradiation in patients given methotrexate after transplantation (relative risk, 3.2; p less than 0.03). The risk of developing interstitial pneumonitis ranged from 8% in patients with none of these adverse risk factors to 94% in patients with all six. These findings may help to identify patients at high risk for this complication.

  2. About Alzheimer's Disease: Risk Factors and Prevention

    MedlinePlus

    ... About ADEAR About Alzheimer's Disease: Risk Factors and Prevention We can’t control some risk factors for ... as well. NIA Information on Risk Factors and Prevention 2014-2015 Alzheimer's Disease Progress Report: Advancing Research ...

  3. In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences.

    PubMed Central

    van Beuningen, H M; van der Kraan, P M; Arntz, O J; van den Berg, W B

    1994-01-01

    OBJECTIVES--Transforming growth factor-beta (TGF-beta) has been shown to antagonise interleukin-1 (IL-1) effects in different systems. Investigations were carried out to study whether TGF-beta 1 modulates IL-1 induced inflammation and IL-1 effects on articular cartilage in the murine knee joint. METHODS--IL-1, TGF-beta 1 or both factors together were injected into the knee joint. Inflammation was studied in whole knee histological sections. Patellar cartilage proteoglycan synthesis was measured using 35S-sulphate incorporation while patellar cartilage glycosaminoglycan content was determined with automated image analysis on joint sections. RESULTS--Co-injection of TGF-beta 1 and IL-1 resulted in synergistic attraction of inflammatory cells. In contrast, TGF-beta 1 counteracted IL-1 induced suppression of articular cartilage proteoglycan synthesis. Proteoglycan depletion was similar shortly after the last injection of IL-1 or IL-1/TGF-beta 1, but accelerated recovery was found with the combination at later days. This protective effect of TGF-beta 1 could not be demonstrated in older mice. CONCLUSIONS--TGF-beta 1 aggravates IL-1 induced knee joint inflammation, but counteracts the deleterious effects of IL-1 on articular cartilage proteoglycan synthesis and content. The data indicate that TGF-beta 1 could play an important part in articular cartilage restoration after IL-1 induced proteoglycan depletion. Images PMID:7979598

  4. Environmental risk factors for osteoporosis

    SciTech Connect

    Goyer, R.A.; Korach, K.S. ); Epstein, S. ); Bhattacharyya, M. ); Pounds, J. )

    1994-04-01

    Environmental risk factors for osteoporosis were reviewed at a conference held at the National Institute for Environmental Health Sciences 8-9 November 1993. The conference was co-sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Disease and the NIH Office of Research in Women's Health. The objective of the conference was to review what is known about risk factors for osteoporosis and to identify gaps in the present state of knowledge that might be addressed by future research. The conference was divided into two broad themes. The first session focused on current knowledge regarding etiology, risk factors, and approaches to clinical and laboratory diagnosis. This was followed by three sessions in which various environmental pollutants were discussed. Topics selected for review included environmental agents that interfere with bone and calcium metabolism, such as the toxic metals lead, cadmium, aluminum, and fluoride, natural and antiestrogens, calcium, and vitamin D.

  5. Age-Related Nuclear Translocation of P2X6 Subunit Modifies Splicing Activity Interacting with Splicing Factor 3A1

    PubMed Central

    Díaz-Hernández, Juan Ignacio; Sebastián-Serrano, Álvaro; Gómez-Villafuertes, Rosa

    2015-01-01

    P2X receptors are ligand-gated ion channels sensitive to extracellular nucleotides formed by the assembling of three equal or different P2X subunits. In this work we report, for the first time, the accumulation of the P2X6 subunit inside the nucleus of hippocampal neurons in an age-dependent way. This location is favored by its anchorage to endoplasmic reticulum through its N-terminal domain. The extracellular domain of P2X6 subunit is the key to reach the nucleus, where it presents a speckled distribution pattern and is retained by interaction with the nuclear envelope protein spectrin α2. The in vivo results showed that, once inside the nucleus, P2X6 subunit interacts with the splicing factor 3A1, which ultimately results in a reduction of the mRNA splicing activity. Our data provide new insights into post-transcriptional regulation of mRNA splicing, describing a novel mechanism that could explain why this process is sensitive to changes that occur with age. PMID:25874565

  6. A Heart That Beats for 500 Years: Age-Related Changes in Cardiac Proteasome Activity, Oxidative Protein Damage and Expression of Heat Shock Proteins, Inflammatory Factors, and Mitochondrial Complexes in Arctica islandica, the Longest-Living Noncolonial Animal

    PubMed Central

    Sosnowska, Danuta; Richardson, Chris; Sonntag, William E.; Csiszar, Anna; Ridgway, Iain

    2014-01-01

    Study of negligibly senescent animals may provide clues that lead to better understanding of the cardiac aging process. To elucidate mechanisms of successful cardiac aging, we investigated age-related changes in proteasome activity, oxidative protein damage and expression of heat shock proteins, inflammatory factors, and mitochondrial complexes in the heart of the ocean quahog Arctica islandica, the longest-lived noncolonial animal (maximum life span potential: 508 years). We found that in the heart of A. islandica the level of oxidatively damaged proteins did not change significantly up to 120 years of age. No significant aging-induced changes were observed in caspase-like and trypsin-like proteasome activity. Chymotrypsin-like proteasome activity showed a significant early-life decline, then it remained stable for up to 182 years. No significant relationship was observed between the extent of protein ubiquitination and age. In the heart of A. islandica, an early-life decline in expression of HSP90 and five mitochondrial electron transport chain complexes was observed. We found significant age-related increases in the expression of three cytokine-like mediators (interleukin-6, interleukin-1β, and tumor necrosis factor-α) in the heart of A. islandica. Collectively, in extremely long-lived molluscs, maintenance of protein homeostasis likely contributes to the preservation of cardiac function. Our data also support the concept that low-grade chronic inflammation in the cardiovascular system is a universal feature of the aging process, which is also manifest in invertebrates. PMID:24347613

  7. Risk Factors For Chronic Rhinosinusitis

    PubMed Central

    Min, Jin-Young; Tan, Bruce K.

    2015-01-01

    Purpose of review To review the recent literature on risk factors for chronic rhinosinusitis (CRS) with an emphasis on genetic, comorbid diseases and environmental factors associated with CRS. Through identifying potential risk factors for CRS, we glean insights into the underlying pathogenic mechanisms and essential for developing effective therapeutic strategies. Recent findings Recent findings demonstrate that genetics, comorbid medical conditions including airway diseases, gastroesophageal reflux disease, inflammatory and autoimmune diseases and various demographic and environmental factors are associated with having a CRS diagnosis. Limitations of current studies include, variable application of disease definitions, lack of prospective longitudinal studies and a disproportionate focus on tertiary care populations. Summary CRS has a broad spectrum of associations ranging from genetics to comorbid diseases and environmental factors. These predisposing factors provide valuable information for possible designing therapeutic and preventive interventions. However, to better understand whether these associations cause CRS, further studies are needed to independently replicate findings, establish temporal relationships between exposure and disease onset, evaluate the influence of exposure dose on disease severity, and to understand the biological effects of these risk factors in the context of CRS. PMID:25479315

  8. Upregulation of the vascular endothelial growth factor, Flt-1, in rat hippocampal neurons after envenoming by Phoneutria nigriventer; age-related modulation.

    PubMed

    Mendonça, Monique Culturato Padilha; Siqueira Soares, Edilene; Miguel Stávale, Leila; Pierre Irazusta, Silvia; da Cruz-Höfling, Maria Alice

    2012-09-15

    This study characterizes the distribution and quantifies the expression of the tyrosine kinase receptor for the vascular endothelial growth factor (VEGF), Flt-1, in the rat hippocampus following intra-peritoneal injection of Phoneutria nigriventer venom (PNV). Post-natal day 14 (P14) and 8-10 weeks (adult) old rats were used and analyses were done at 1, 2, 5 and 24 h after venom exposure and compared with saline-injected counterparts. PNV-injected animals showed hippocampal venules with perivascular edema indicating blood-brain barrier (BBB) dysfunction. This was accompanied by significant overexpression of Flt-1 which though was not the same for CA1, CA2, CA3 and dentate gyrus (DG) hippocampal regions, neither for P14 and adult rats. Regional analysis using GIMP methodology showed that Flt-1 was constitutively distributed more densely in neurons of DG, followed by CA1/CA2 and CA3 of both control P14 and adult animals, without variation over time, but significantly more expressed in P14 than in adults. A time-course analysis showed that Flt-1 upregulation was progressive and that neurons VEGFR1/Flt-1+ of PNV-exposed animals are timely and regionally modulated depending on the hippocampal region, being CA2 the least responsive region regardless animal's age, whilst DG was the most susceptible with adult animals having higher upregulation than neonates. Since VEGF has been reported to confer protection in several pathological processes we suggest that VEGF may be involved in hippocampal neurons response via Flt-1 mediation following PNV envenoming; its higher upregulation in adult envenomed rats may be an indication that Flt-1 neuroprotective mediation is more efficient with age. The Flt-1 upregulation and the incidence of perivascular edema in young animals may indicate a pro-inflammatory role of the receptor. PMID:22659541

  9. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    PubMed Central

    Ragazzo, Michele; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Luigi Tonino; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression. PMID:25478207

  10. Sexual harassment: identifying risk factors.

    PubMed

    O'Hare, E A; O'Donohue, W

    1998-12-01

    A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures. PMID:9883305

  11. [Psoriasis and cardiovascular risk factors].

    PubMed

    Tal, Roy; Pavlovsky, Lev; David, Michael

    2012-10-01

    Psoriasis is a common inflammatory skin disease which may dramatically affect patients' lives. This chronic disease is characterized by a protracted course of alternating remissions and relapses. In recent years, the attention of researchers has focused on the association between psoriasis and cardiovascular disease risk factors. This review summarizes the literature on this topic with an emphasis on research conducted in Israel. PMID:23316664

  12. Targeting MAPK Signaling in Age-Related Macular Degeneration

    PubMed Central

    Kyosseva, Svetlana V.

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease. PMID:27385915

  13. Age-Related Factors That Influence Fertility

    MedlinePlus

    ... pressure Diabetes Thyroid disease Infection in the uterus PCOS Antiphospholipid syndrome, an autoimmune disorder caused when immune ... male fertility, NIH study suggests Some women with PCOS may have adrenal disorder, NIH researchers suggest Weight ...

  14. Parainflammation, chronic inflammation and age-related macular degeneration

    PubMed Central

    Chen, Mei; Xu, Heping

    2016-01-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

  15. VITAMIN D DEFICIENCY IN NEOVASCULAR VERSUS NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

    PubMed Central

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W.; Stinnett, Sandra S.; Vajzovic, Lejla M.; Mruthyunjaya, Prithvi

    2014-01-01

    Purpose To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Methods Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Results Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non–age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18– 0.68) odds ratio for NVAMD. Conclusion This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD. PMID:24946100

  16. Risk factors for postoperative ileus

    PubMed Central

    Kutun, Suat; Ulucanlar, Haluk; Tarcan, Oguz; Demir, Abdullah; Cetin, Abdullah

    2011-01-01

    Purpose This study aimed to examine extended postoperative ileus and its risk factors in patients who have undergone abdominal surgery, and discuss the techniques of prevention and management thereof the light of related risk factors connected with our study. Methods This prospective study involved 103 patients who had undergone abdominal surgery. The effects of age, gender, diagnosis, surgical operation conducted, excessive small intestine manipulation, opioid analgesic usage time, and systemic inflammation on the time required for the restoration of intestinal motility were investigated. The parameters were investigated prospectively. Results Regarding the factors that affected the restoration of gastrointestinal motility, resection operation type, longer operation period, longer opioid analgesics use period, longer nasogastric catheter use period, and the presence of systemic inflammation were shown to retard bowel motility for 3 days or more. Conclusion Our study confirmed that unnecessary analgesics use in patients with pain tolerance with non-steroid anti-inflammatory drugs, excessive small bowel manipulation, prolonged nasogastric catheter use have a direct negative effect on gastrointestinal motility. Considering that an exact treatment for postoperative ileus has not yet been established, and in light of the risk factors mentioned above, we regard that prevention of postoperative ileus is the most effective way of coping with intestinal dysmotility. PMID:22111079

  17. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  18. Gene–gene interaction of CFH, ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population

    PubMed Central

    Huang, L; Meng, Q; Zhang, C; Sun, Y; Bai, Y; Li, S; Deng, X; Wang, B; Yu, W; Zhao, M; Li, X

    2015-01-01

    Purpose To evaluate the association and interaction of five single-nucleotide polymorphisms (SNPs) in three genes (CFH, ARMS2, and ARMS2/HTRA1) with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese population. Methods A total of 300 nAMD and 300 PCV patients and 301 normal subjects participated in the present study. The allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene–gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction (MDR) method. Results The risk alleles of CFH rs800292, rs2274700, ARMS2 rs3057847, and ARMS2/HTRA1 rs3793917 showed significant difference between nAMD or PCV patients and controls (all P<0.01). The homozygosity of risk alleles for rs800292, rs2274700, rs3750847, and rs3793917 were significantly different between nAMD patients and controls (all P<0.01), and predisposed to PCV patients (all P<0.01). After cross-validation consistency (CVC) and permutation tests, the two-locus model rs2274700_rs3750847 has a balanced accuracy of 64.37% in predicting nAMD disease risk. The one-marker model, rs3750847, and two-locus model rs2274700_rs3750847 has a balanced accuracy of 66.07% and 65.89% in predicting PCV disease risk, respectively. Furthermore, CFH rs1065489 did not show significant association with nAMD (P>0.01), but was strongly associated with PCV in Chinese patients (P<0.001). Conclusions In this study, we found that the interaction of ARMS2 and ARMS2/HTRA1 is significantly associated with nAMD, and the interaction of CFH and ARMS2 is pronounced in PCV development in Chinese population. PMID:25771815

  19. [Environmental Risk Factors for Dementia].

    PubMed

    Tashiro, Yoshitaka; Kinoshita, Ayae

    2016-07-01

    Owing to recent advancements in imaging techniques and biomarker research, the natural history of Alzheimer's disease (AD) has become clear from the very first preclinical stage. According to the study, more than 20 years before the onset of AD, Aβ starts to accumulate in the brain. This induces neurofibrillary tangle formation in the cerebral isocortex, leading to cognitive decline. If this process is suppressed, disease activity can be controlled. However, at this point, the best and most realistic way to deal with AD is to target the environmental factors that have been identified as risk factors by epidemiological studies. PMID:27395468

  20. Human factors and risk assessment

    SciTech Connect

    Al-Minhali, A.

    1996-11-01

    A case study was presented in the 1994 Abu Dhabi International Exhibition and Conference (ADIPEC, 94) which discussed the importance of investigating human factors in the design of a high integrity protection system (HIPS) to be installed on an offshore high pressure gas platform, (SPE reference ADSPE 80). This paper will follow up on the design changes, installation and operation of the HIPS with emphasis on practical implications as a result of improper integration of human factors in the system reliability and risk assessment studies.

  1. Risk Factors for β-Amyloid Deposition in Healthy Aging

    PubMed Central

    Rodrigue, Karen M.; Rieck, Jennifer R.; Kennedy, Kristen M.; Devous, Michael D.; Diaz-Arrastia, Ramon; Park, Denise C.

    2013-01-01

    Importance Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection. Objective To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Specifically, we hypothesized that individuals with a vascular risk factor such as hypertension, in combination with a genetic risk factor for Alzheimer disease (apolipoprotein E ε4 allele), would show greater amyloid burden than those without such risk. Design Cross-sectional study. Setting General community. Participants One hundred eighteen well-screened and cognitively normal adults, aged 47 to 89 years. Participants were classified in the hypertension group if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic, as measured across 7 occasions at the time of study. Intervention Participants underwent Aβ positron emission tomography imaging with radiotracer fluorine 18–labeled florbetapir. Participants were genotyped for apolipoprotein E and were classified as ε4+ or ε4−. Main Outcome Measure Amyloid burden. Results Participants in the hypertension group with at least 1 ε4 allele showed significantly greater amyloid burden than those with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure was strongly associated with increased mean cortical amyloid level for subjects with at least 1 ε4 allele. Conclusions and Relevance Vascular disease is a prevalent age-related condition that is highly responsive to both behavioral modification and medical treatment. Proper control and prevention of risk factors such as hypertension earlier in the life span may be one potential mechanism to ameliorate or delay neuropathological brain changes with aging. PMID:23553344

  2. [Suicide - background, epidemiology, risk factors].

    PubMed

    Ajdacic-Gross, Vladeta

    2015-10-01

    Suicide research, in particular epidemiology, comprises a huge amount of data. However, the theoretical understanding clearly lags behind the empirical knowledge. Suicide, suicide attempts and other suicidal behaviors are more heterogeneous than most explanatory approaches would assume. The most important recent contributions to a better understanding have come from selected epidemiological findings and, interestingly, prevention. This article provides an overview of epidemiological findings, the most relevant risk factors and conclusions related to successful preventive efforts. PMID:26423878

  3. Drusen maculopathy: a risk factor for visual deterioration.

    PubMed

    Algvere, Peep V; Kvanta, Anders; Seregard, Stefan

    2016-08-01

    Age-related macular degeneration (AMD), the most common cause of visual loss after the age of 65, displays a degeneration of the retinal pigment epithelial (RPE) cells and photoreceptors in the retinal centre (macula). The central macula (fovea) that contains mostly cone photoreceptors mediates the high visual acuity. Drusen maculopathy may lead to visual deterioration. Drusen are extracellular deposits of debris that accumulate on Bruch's membrane. Drusen attract inflammatory, immunological and vasoactive stimuli. RPE and photoreceptor cells overlying drusen exhibit biochemical and morphological signs of degeneration. Strong and intermittent light exposure (photons) induces the formation of free radicals in the very high oxygen tension milieu of the retina. The negative effects of irradiation stimulate accumulation of lipofuscin in RPE and photoreceptor cells leading to mitochondrial dysfunction and apoptotic cell death. A hydrophobic barrier is built up in Bruch's membrane reducing diffusion to the choroid. Hereditary and inflammatory factors modify the risk for AMD. There is a genetic dysregulation of the complement system leading to inappropriate complement activation. The genetic polymorphism of complement factor H (CFH) and age-related maculopathy susceptibilty 2 (ARMS2) increase the risk of progression to advanced AMD. The photoelectric effect creates free radicals, resulting in a continuous increase of lipofuscin formation and impairing mitochondrial activity. In addition, inflammation and complement dysregulation contribute to the formation of drusen and vasoproliferative reactions with neovascularization. Antioxidants neutralize reactive oxygen species and reduce lipofuscin accumulation in RPE and photoreceptor cells. For prophylactic treatment of drusen maculopathy, high doses of antioxidants such as vitamins C and E, lutein, zeaxanthine and zinc are used according to the Age-Related Eye Disease Study 2 (AREDS 2). The risk of developing advanced AMD was

  4. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  5. Long noncoding RNAs in aging and age-related diseases.

    PubMed

    Kour, Sukhleen; Rath, Pramod C

    2016-03-01

    Aging is the universal, intrinsic, genetically-controlled, evolutionarily-conserved and time-dependent intricate biological process characterised by the cumulative decline in the physiological functions and their coordination in an organism after the attainment of adulthood resulting in the imbalance of neurological, immunological and metabolic functions of the body. Various biological processes and mechanisms along with altered levels of mRNAs and proteins have been reported to be involved in the progression of aging. It is one of the major risk factors in the patho-physiology of various diseases and disorders. Recently, the discovery of pervasive transcription of a vast pool of heterogeneous regulatory noncoding RNAs (ncRNAs), including small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs), in the mammalian genome have provided an alternative way to study and explore the missing links in the aging process, its mechanism(s) and related diseases in a whole new dimension. The involvement of small noncoding RNAs in aging and age-related diseases have been extensively studied and recently reviewed. However, lncRNAs, whose function is far less explored in relation to aging, have emerged as a class of major regulators of genomic functions. Here, we have described some examples of known as well as novel lncRNAs that have been implicated in the progression of the aging process and age-related diseases. This may further stimulate research on noncoding RNAs and the aging process. PMID:26655093

  6. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  7. Age-Related Tissue Stiffening: Cause and Effect

    PubMed Central

    Sherratt, Michael J.

    2013-01-01

    Significance Tissue elasticity is severely compromised in aging skin, lungs, and blood vessels. In the vascular and pulmonary systems, respectively, loss of mechanical function is linked to hypertension, which in turn is a risk factor for heart and renal failure, stroke, and aortic aneurysms, and to an increased risk of mortality as a result of acute lung infections. Recent Advances Although cellular mechanisms were thought to play an important role in mediating tissue aging, the reason for the apparent sensitivity of elastic fibers to age-related degradation remained unclear. We have recently demonstrated that compared with type I collagen, a key component of the elastic fiber system, the cysteine-rich fibrillin microfibril is highly susceptible to direct UV exposure in a cell-free environment. We hypothesized therefore that, as a consequence of both their remarkable longevity and cysteine-rich composition, many elastic fiber-associated components will be susceptible to the accumulation of damage by both direct UV radiation and reactive oxygen species-mediated oxidation. Critical Issues Although elastic fiber remodeling is a common feature of aging dynamic tissues, the inaccessibility of most human tissues has hampered attempts to define the molecular causes. Clinical Care Relevance Although, currently, the localized repair of damaged elastic fibers may be effected by the topical application of retinoids and some cosmetic products, future studies may extend the application of systemic transforming growth factor β antagonists, which can prevent cardiovascular remodeling in murine Marfan syndrome, to aging humans. Acellular mechanisms may be key mediators of elastic fiber remodeling and hence age-related tissue stiffening. PMID:24527318

  8. Modifications of Coronary Risk Factors

    PubMed Central

    Albu, Jeanine; Gottlieb, Sheldon H.; August, Phyllis; Nesto, Richard W.; Orchard, Trevor J.

    2009-01-01

    In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers. PMID:16813737

  9. Age-related somatic mutations in the cancer genome

    PubMed Central

    Milholland, Brandon; Auton, Adam; Suh, Yousin; Vijg, Jan

    2015-01-01

    Aging is associated with an increased risk of cancer, possibly in part because of an age-related increase in mutations in normal tissues. Due to their extremely low abundance, somatic mutations in normal tissues frequently escape detection. Tumors, as clonal expansions of single cells, can provide information about the somatic mutations present in these cells prior to tumorigenesis. Here, we used data from The Cancer Genome Atlas (TCGA), to systematically study the frequency and spectrum of somatic mutations in a total of 6,969 patients and 34 different tumor types as a function of the age of the patient. After using linear modeling to control for the age structure of different tumor types, we found that the number of identified somatic mutations increases exponentially with age. Using additional data from the literature, we found that accumulation of somatic mutations is associated with cell division rate, cancer risk and cigarette smoking, with the latter also associated with a distinct spectrum of mutations. Our results confirm that aging is associated with the accumulation of somatic mutations, and strongly suggest that the level of genome instability of normal cells, modified by both endogenous and environmental factors, is the main risk factor for cancer. PMID:26384365

  10. Risk factors identified for certain lymphoma subtypes

    Cancer.gov

    In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11

  11. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    PubMed

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

  12. Coronary risk factors in schoolchildren.

    PubMed Central

    Boreham, C; Savage, J M; Primrose, D; Cran, G; Strain, J

    1993-01-01

    Death rates from coronary heart disease (CHD) in Northern Ireland are among the highest in the world. However, no data have been available to test the hypothesis that the high prevalence of CHD is reflected by the risk status of the childhood population. A randomly selected 2% population sample of 1015 children aged 12 and 15 years was studied to obtain baseline information on blood pressure, lipid profile, cigarette smoking, family history, physical activity, cardiorespiratory fitness, and dietary fat intake. Using available criteria thresholds, 15-23% displayed increased blood pressure, 12-25% had unfavourable lipid profiles, and 18-34% were overfat. In 15 year old children, 16-21% admitted being regular smokers, 26-34% displayed poor cardiorespiratory fitness, and 24-29% reported little physical activity in the previous week. Dietary analysis revealed relatively low polyunsaturated to saturated fatty acid ratios and high mean fat intakes, accounting for approximately 40% total daily energy. Despite the exclusion of family history from the analysis, 16% of the older children exhibited three or more risk factors. These results justify major concern about the level of potential coronary risk in Northern Ireland schoolchildren. Broadly based primary prevention strategies aimed at children are essential if future adult CHD mortality is to be reduced. PMID:8481039

  13. Cardiovascular risk factors among Chamorros

    PubMed Central

    Chiem, Binh; Nguyen, Victoria; Wu, Phillis L; Ko, Celine M; Cruz, Lee Ann; Sadler, Georgia Robins

    2006-01-01

    Background Little is known regarding the cardiovascular disease risk factors among Chamorros residing in the United States. Methods The Chamorro Directory International and the CDC's Behavioral Risk Factor Surveillance System Questionnaire (BRFSS) were used to assess the health related practices and needs of a random sample of 228 Chamorros. Results Inactivity, hypertension, elevated cholesterol and diabetes mellitus were more prevalent in this Chamorro sample compared to the US average. Participants who were 50-and-older or unemployed were more likely to report hypertension, diabetes and inactivity, but they were also more likely to consume more fruits and vegetables than their younger and employed counterparts. Women were more likely to report hypertension and diabetes, whereas men were more likely to have elevated BMI and to have never had their blood cholesterol checked. Conclusion The study provides data that will help healthcare providers, public health workers and community leaders identify where to focus their health improvement efforts for Chamorros and create culturally competent programs to promote health in this community. PMID:17156462

  14. Configurations of Common Childhood Psychosocial Risk Factors

    ERIC Educational Resources Information Center

    Copeland, William; Shanahan, Lilly; Costello, E. Jane; Angold, Adrian

    2009-01-01

    Background: Co-occurrence of psychosocial risk factors is commonplace, but little is known about psychiatrically-predictive configurations of psychosocial risk factors. Methods: Latent class analysis (LCA) was applied to 17 putative psychosocial risk factors in a representative population sample of 920 children ages 9 to 17. The resultant class…

  15. Concurrent Risk Factors for Adolescent Violence.

    ERIC Educational Resources Information Center

    Saner, Hilary; Ellickson, Phyllis

    1996-01-01

    Examines the risk and protective factors for different types of violent behavior in high school adolescents. Major risk factors include gender and deviant behaviors, committing nonviolent felonies, academic failure, and lack of parental affection and support. As risk factors increase, the likelihood of violent behavior increases. Impaired parental…

  16. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  17. Age-specific risk factors for lead absorption in children

    SciTech Connect

    Walter, S.D.; Yankel, A.J.; von Lindern, I.H.

    1980-01-01

    The relationship of blood lead levels to environmental and individual characteristics is analyzed in a large sample of children residing near a lead smelting complex, with particular emphasis on the identification of age-related risk factors. Exceptional variation in both blood leads and its determinants within the study region facilitated the simultaneous detection of several significant risk factors for each year of age from 1 to 9 y. The strongest predictor of blood lead at all ages was air lead, but the secondary risk factors were age dependent. Household dustiness was significantly related to blood lead in young children, especially those under 2 y of age; soil lead may be an important source of ingested lead for children between 2 and 7 y. Other significant effects included that of pica at about 2 y of age, a slight effect of the occupational category of the fathers of 5- to 8-y-old children, and a tendency for 8- and 9-y-old boys to have higher blood leads than girls of the same age. Lead concentration in household paint was not a significant risk factor. These results suggest that a multifactorial approach to the prevention of excessive lead absorption by children is required.

  18. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  19. Proinflammatory cytokines, aging, and age-related diseases.

    PubMed

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. PMID:23792036

  20. Prevalence of age-related macular degeneration among the elderly

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Zarghami, Amin; Hosseini, Seyed Reza; Rajaee, Neda; Rasoulinejad, Seyed Elahe; Mikaniki, Ebrahim

    2015-01-01

    Background: Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in elderly population in the developing countries. Previous epidemiological studies revealed various potential modifiable risk factors for this disease. The purpose of this study was to evaluate the prevalence of AMD among elderly living in Babol, North of Iran. Methods: The study population of this cross-sectional study came from the Amirkola Health and Ageing Project (AHAP), the first comprehensive cohort study of the health of people aged 60 years and over in Amirkola, North of Iran. The prevalence of AMD was estimated and its risk was determined using logistic regression analysis (LRA) with regard to variables such as smoking, hyperlipidemia, hypertension and diabetes. Results: Five hundred and five participants with mean age of 71.55±5.9 (ranged 60-89) years entered the study. The prevalence of AMD was 17.6%. There was a significant association between AMD and smoking (P<0.001) but no association was seen with AMD and age, level of education, history of hyperlipidemia, hypertension and diabetes. Multiple LRAs revealed that smoking increased AMD by odds ratio of 5.03 (95% confidence interval 2.47-10.23 p<0.001) as compared to nonsmokers Conclusion: According to our findings, the prevalence of AMD was relatively high and smoking increased the risk of AMD in the elderly population. PMID:26644880

  1. Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide. Genetics and diet contribute to the relative risk for developing AMD, but their interactions are poorly understood. Genetic variations in Complement Factor H (CFH), and dietary glycemic index (GI) are major ris...

  2. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  3. Age-Related Changes in Creative Thinking

    ERIC Educational Resources Information Center

    Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

    2008-01-01

    Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

  4. Inflammatory networks in ageing, age-related diseases and longevity.

    PubMed

    Vasto, Sonya; Candore, Giuseppina; Balistreri, Carmela Rita; Caruso, Marco; Colonna-Romano, Giuseppina; Grimaldi, Maria Paola; Listi, Florinda; Nuzzo, Domenico; Lio, Domenico; Caruso, Calogero

    2007-01-01

    Inflammation is considered a response set by the tissues in response to injury elicited by trauma or infection. It is a complex network of molecular and cellular interactions that facilitates a return to physiological homeostasis and tissue repair. The individual response against infection and trauma is also determined by gene variability. Ageing is accompanied by chronic low-grade inflammation state clearly showed by 2-4-fold increase in serum levels of inflammatory mediators. A wide range of factors has been claimed to contribute to this state; however, the most important role seems to be played by the chronic antigenic stress, which affects immune system thorough out life with a progressive activation of macrophages and related cells. This pro-inflammatory status, interacting with the genetic background, potentially triggers the onset of age-related inflammatory diseases as atherosclerosis. Thus, the analysis of polymorphisms of the genes that are key nodes of the natural immunity response might clarify the patho-physiology of age-related inflammatory diseases as atherosclerosis. On the other hand, centenarians are characterized by marked delay or escape from age-associated diseases that, on average, cause mortality at earlier ages. In addition, centenarian offspring have increased likelihood of surviving to 100 years and show a reduced prevalence of age-associated diseases, as cardiovascular disease (CVD) and less prevalence of cardiovascular risk factors. So, genes involved in CVD may play an opposite role in human longevity. Thus, the model of centenarians can be used to understand the role of these genes in successful and unsuccessful ageing. Accordingly, we report the results of several studies in which the frequencies of pro-inflammatory alleles were significantly higher in patients affected by infarction and lower in centenarians whereas age-related controls displayed intermediate values. These findings point to a strong relationship between the genetics

  5. Contribution of the Nurses’ Health Study to the Epidemiology of Cataract, Age-Related Macular Degeneration, and Glaucoma

    PubMed Central

    Wu, Juan; Cho, Eunyoung; Ogata, Soshiro; Jacques, Paul; Taylor, Allen; Chiu, Chung-Jung; Wiggs, Janey L.; Seddon, Johanna M.; Hankinson, Susan E.; Schaumberg, Debra A.; Pasquale, Louis R.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) to understanding the genetic and lifestyle factors that influence the risk of cataract, age-related macular degeneration, and glaucoma. Methods. We performed a narrative review of the publications of the NHS between 1976 and 2016. Results. The NHS has helped to elucidate the roles of genetics, lifestyle factors (e.g., cigarette smoking associated with cataract extraction and age-related macular degeneration), medical conditions (e.g., diabetes associated with cataract extraction and glaucoma), and dietary factors (e.g., greater carotenoid intake and lower glycemic diet associated with lower risk of age-related macular degeneration) in the etiology of degree and progression of lens opacities, cataract extraction, age-related macular degeneration, primary open-angle glaucoma, and exfoliation glaucoma. Conclusions. The findings from the NHS, combined with those of other studies, have provided compelling evidence to support public health recommendations for helping to prevent age-related eye diseases: abstinence from cigarette smoking, maintenance of healthy weight and diabetes prevention, and a healthy diet rich in fruits and vegetables. PMID:27459452

  6. APOLIPOPROTEIN E GENE AND EARLY AGE-RELATED MACULOPATHY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants from the Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 ye...

  7. Nutritional antioxidants and age-related cataract and maculopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Loss of vision is the second greatest, next to death, fear among the elderly. Age-related cataract (ARC) and maculopathy (ARM) are two major causes of blindness worldwide. There are several important reasons to study relationships between risk for ARC/ARM and nutrition: (1) because it is likely that...

  8. [Suicide risk factors among the elderly].

    PubMed

    Pérez Barrero, Sergio Andrés

    2012-08-01

    The author offers a brief overview of suicide risk factors among the elderly such as depression, all manner of abuse of the elderly, as well as medical, psychological and social risk factors, etc. By way of conclusion, a practical guide to evaluate suicide risk among the elderly is provided. PMID:22899142

  9. Family Factors Predicting Categories of Suicide Risk

    ERIC Educational Resources Information Center

    Randell, Brooke P.; Wang, Wen-Ling; Herting, Jerald R.; Eggert, Leona L.

    2006-01-01

    We compared family risk and protective factors among potential high school dropouts with and without suicide-risk behaviors (SRB) and examined the extent to which these factors predict categories of SRB. Subjects were randomly selected from among potential dropouts in 14 high schools. Based upon suicide-risk status, 1,083 potential high school…

  10. Chlamydia infection status, genotype, and age-related macular degeneration

    PubMed Central

    Khandhadia, Sam; Foster, Sebastian; Cree, Angela; Griffiths, Helen; Osmond, Clive; Goverdhan, Srinivas

    2012-01-01

    Purpose To evaluate whether Chlamydia (C.) infections are associated with age-related macular degeneration (AMD) and to assess if this association is influenced by the complement factor H (CFH) Y402H or the high temperature requirement A serine peptidase 1 (HTRA1) rs11200638 risk genotypes. Methods One hundred ninety-nine AMD patients with early and late forms of the disease and 100 unaffected controls, at least 50 years old were included in the study. Patients in the AMD and control groups were selected based on known CFH Y402H variant genotype status (one third homozygous CC, one third heterozygous CT, and one third wild-type TT). Plasma from all patients and controls was tested for C. pneumoniae, C. trachomatis, and C. psittaci IgG seropositivity using a micro-immunofluorescent assay to establish previous infection status. Assays were conducted blind to risk genotypes and the results analyzed using univariate and multivariate (logistic regression) analysis. Results IgG seropositivity to C. pneumoniae was most prevalent (69.2%, n=207), followed by C. trachomatis (7.4%, n=22) and C. psittaci (3.3%, n=10). No association was found between each of the three Chlamydia species IgG seropositivity and AMD status or severity (early/late). There was also no significant association between Chlamydia species IgG seropositivity and AMD status or severity, in patients carrying at least one CFH Y402H risk allele (C) or HTRA1 rs11200638 risk allele (A), with univariate or logistic regression analysis. Conclusions Chlamydia infection status does not appear to be associated with AMD status or severity. The presence of CFH Y402H and HTRA1 rs11200638 risk genotypes does not alter this negative association. PMID:22259222

  11. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System.

    PubMed

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-02-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere's disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  12. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    PubMed Central

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  13. Age-related oxidative modifications of transthyretin modulate its amyloidogenicity

    PubMed Central

    Zhao, Lei; Buxbaum, Joel N; Reixach, Natàlia

    2013-01-01

    The transthyretin amyloidoses are diseases of protein misfolding characterized by the extracellular deposition of fibrils and other aggregates of the homotetrameric protein transthyretin (TTR) in peripheral nerves, heart and other tissues. Age is the major risk factor for the development of these diseases. We hypothesized that an age-associated increase in protein oxidation could be involved in the onset of the senile forms of the TTR amyloidoses. To test this hypothesis we have produced and characterized relevant age-related oxidative modifications of wild type (WT) and the Val122Ile (V122I) TTR variant, both involved in cardiac TTR deposition in the elderly. Our studies show that methionine/cysteine oxidized TTR and carbonylated TTR either from WT or the V122I variant, are thermodynamically less stable than their non-oxidized counterparts. Moreover, carbonylated WT and carbonylated V122I TTR have a greater propensity to form aggregates and fibrils than WT and V122I TTR, respectively, at physiologically attainable pH. It is well known that TTR tetramer dissociation, the limiting step for aggregation and amyloid fibril formation, can be prevented by small molecules that bind the TTR tetramer interface. Here, we report that carbonylated WT TTR is less amenable to resveratrol-mediated tetramer stabilization than WT TTR. All the oxidized forms of TTR tested are cytotoxic to a human cardiomyocyte cell line known to be a target for cardiac-specific TTR variants. Overall these studies demonstrate that age-related oxidative modifications of TTR can contribute to the onset of the senile forms of the TTR amyloidoses. PMID:23414091

  14. Age-related oxidative modifications of transthyretin modulate its amyloidogenicity.

    PubMed

    Zhao, Lei; Buxbaum, Joel N; Reixach, Natàlia

    2013-03-19

    The transthyretin amyloidoses are diseases of protein misfolding characterized by the extracellular deposition of fibrils and other aggregates of the homotetrameric protein transthyretin (TTR) in peripheral nerves, heart, and other tissues. Age is the major risk factor for the development of these diseases. We hypothesized that an age-associated increase in the level of protein oxidation could be involved in the onset of the senile forms of the TTR amyloidoses. To test this hypothesis, we have produced and characterized relevant age-related oxidative modifications of the wild type (WT) and the Val122Ile (V122I) TTR variant, both involved in cardiac TTR deposition in the elderly. Our studies show that methionine/cysteine-oxidized TTR and carbonylated TTR from either the WT or the V122I variant are thermodynamically less stable than their nonoxidized counterparts. Moreover, carbonylated WT and carbonylated V122I TTR have a stronger propensity to form aggregates and fibrils than WT and V122I TTR, respectively, at physiologically attainable pH values. It is well-known that TTR tetramer dissociation, the limiting step for aggregation and amyloid fibril formation, can be prevented by small molecules that bind the TTR tetramer interface. Here, we report that carbonylated WT TTR is less amenable to resveratrol-mediated tetramer stabilization than WT TTR. All the oxidized forms of TTR tested are cytotoxic to a human cardiomyocyte cell line known to be a target for cardiac-specific TTR variants. Overall, these studies demonstrate that age-related oxidative modifications of TTR can contribute to the onset of the senile forms of the TTR amyloidoses. PMID:23414091

  15. Age-Related Macular Degeneration: Genetics and Biology.

    PubMed

    Kumaramanickavel, Govindasamy

    2016-01-01

    Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Approximately half a dozen physiological and biochemical cascades are disrupted in the AMD disease genesis, eventually leading to the distortion and disruption of the subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen genetic factors have so far been identified, including the recent ones, through powerful genomic technologies and large robust sample sizes. The noteworthy genetic variants (common and rare) are complement factor H, complement factor H-related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous amount of scientific information generated over the years, diagnostic genetic or biomarker tests are still not available for clinicians to understand the natural course of the disease and its management in a patient. However, further research in the field should reduce this gap not only by aiding the clinician but also through the possibilities of clinical intervention with complement pathway-related inhibitors entering preclinical and clinical trials in the near future. PMID:27488064

  16. Risk Factors for High Blood Pressure

    MedlinePlus

    ... the NHLBI on Twitter. Risk Factors for High Blood Pressure Anyone can develop high blood pressure; however, age, ... can increase your risk for developing high blood pressure. Age Blood pressure tends to rise with age. About 65 ...

  17. [General practitioner burnout: risk factors].

    PubMed

    Dagrada, H; Verbanck, P; Kornreich, C

    2011-09-01

    This paper aims to review current knowledge on risk factors leading to burn-out of general practitioners, who are particularly concerned by burn-out, as 50% of them are being more or less affected. This article is based on bibliographic research covering literature between 1975 and 2010, using PUB MED software, medical books and articles. 44 articles were selected as dealing well with the aspects of the burn-out reviewed here. It seems established that stress precedes burnout symptoms. Theories investigating relationships between stress and work are presented. Exogenic stress (load and organization of work, emotional interaction with the patient, constraints, lack of recognition, conflicts between private and professional life) interacts with endogenous stress (idealism, (too much) acute feeling of responsibility, mood disorder, difficulty in collaborating, character, personality). Burn-out symptoms would appear preferentially when these two stresses coexist. Despite the wealth of publications, there is still a lack of knowledge of the causes of burn-out, requiring therefore increased research efforts, in order to improve the implementation of preventive measures, beneficial to the doctors as well as to their patients. PMID:22034773

  18. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  19. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  20. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  1. New era for personalized medicine: the diagnosis and management of age-related macular degeneration

    PubMed Central

    Baird, Paul N; Hageman, Gregory S; Franzco, Robyn H Guymer

    2014-01-01

    It can be argued that age-related macular degeneration is one of the best characterized complex trait diseases. Extensive information related to genetic and environmental risk factors exists, and a number of different biological pathways are strongly implicated in its aetiology. Along with recent improvements in high throughput and relatively inexpensive genetic technologies, we are now in a position to consider developing a presymptomatic, personalized approach towards the assessment, management and treatment of this disease. We explore the applicability and challenges of this approach if it is to become commonplace for guiding treatment decisions for individuals with pre-existing disease or for those at high risk of developing it. PMID:19878229

  2. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  3. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    PubMed

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD. PMID:27348529

  4. Cardiovascular risk factors in Italy.

    PubMed

    Menotti, A

    1999-12-01

    In the 1950s the Italian population was known for its low mean levels of major cardiovascular risk factors and serum cholesterol in particular. A definite increase of those mean levels was associated, in the next 2 decades, with increasing death rates from cardiovascular diseases and coronary heart disease. Between the late 1970s and early 1990s cardiovascular death rates declined by over 40%. Large population surveys showed, between 1978 and 1987, small decreases in the mean levels of blood pressure (in both sexes), of smoking habits (in men), and of body weight (in women), while serum cholesterol remained stable. These changes mathematically explained about two-thirds of the observed decline in cardiovascular mortality among middle-aged people. In the late 1980s and early 1990s scattered population studies suggested a decline in mean population levels of serum cholesterol, at least in some areas of the country. More coordinated or systematic preventive campaigns were organized by the public health authorities. On the other hand activities of many small private organizations dealing with heart health likely explain the spread of knowledge, attitude, and practice in the prevention of cardiovascular diseases. Food industry started to produce low-fat products and to label foods with nutrition facts. Changes in food consumption in the beneficial direction started to be recorded in the late 1980s. The spread of antihypertensive treatment was partly favored by the National Health Service offering anti-hypertensive drugs at relatively low cost. Government regulations have more and more restricted the public areas where smoking is allowed. An increasing interest for prevention on the part of physicians is a recent issue, mainly bound to the success of some major controlled trials of hypocholesterolemic drugs. PMID:10641828

  5. Multiple Interacting Risk Factors: On Methods for Allocating Risk Factor Interactions.

    PubMed

    Price, Bertram; MacNicoll, Michael

    2015-05-01

    A persistent problem in health risk analysis where it is known that a disease may occur as a consequence of multiple risk factors with interactions is allocating the total risk of the disease among the individual risk factors. This problem, referred to here as risk apportionment, arises in various venues, including: (i) public health management, (ii) government programs for compensating injured individuals, and (iii) litigation. Two methods have been described in the risk analysis and epidemiology literature for allocating total risk among individual risk factors. One method uses weights to allocate interactions among the individual risk factors. The other method is based on risk accounting axioms and finding an optimal and unique allocation that satisfies the axioms using a procedure borrowed from game theory. Where relative risk or attributable risk is the risk measure, we find that the game-theory-determined allocation is the same as the allocation where risk factor interactions are apportioned to individual risk factors using equal weights. Therefore, the apportionment problem becomes one of selecting a meaningful set of weights for allocating interactions among the individual risk factors. Equal weights and weights proportional to the risks of the individual risk factors are discussed. PMID:25644783

  6. What Are the Risk Factors for Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... what causes gastrointestinal stromal tumors? What are the risk factors for gastrointestinal stromal tumors? A risk factor is ... disease like cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like ...

  7. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  8. [Lifestyle-related risk factors for dementia].

    PubMed

    Phung, Thien Kieu Thi; Andersen, Kjeld; Kessing, Lars Vedel; Waldemar, Gunhild

    2006-10-01

    Emerging knowledge about modifiable risk factors for dementia has given rise to interventions that can potentially prevent or delay the onset of dementia and the possible target periods for intervention extend from prenatal period to old age. Factors during early life such as nutrition, education, and parental socioeconomic status can influence the development of dementia later in life. From mid to late life, a physically, socially, and intellectually active lifestyle is associated with reduced risk for dementia. Moreover, modification of cardiovascular risk factors during this period can potentially reduce risk for dementia. PMID:17032603

  9. Developmental Risk Factors for Sexual Offending.

    ERIC Educational Resources Information Center

    Lee, Joseph K. P.; Jackson, Henry J.; Pattison, Pip; Ward, Tony

    2002-01-01

    A study involving 64 Australian sex offenders and 33 non-sex offenders found childhood emotional abuse and family dysfunction, childhood behavior problems, and childhood sexual abuse were developmental risk factors for paraphilia. Emotional abuse and family dysfunction was found to be a risk factor for pedophilia, exhibitionism, rape, or multiple…

  10. Risk factors across the eating disorders.

    PubMed

    Hilbert, Anja; Pike, Kathleen M; Goldschmidt, Andrea B; Wilfley, Denise E; Fairburn, Christopher G; Dohm, Faith-Anne; Walsh, B Timothy; Striegel Weissman, Ruth

    2014-12-15

    This study sought to examine risk and onset patterns in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Women with AN (n=71), BN (n=66), BED (n=160) and non-psychiatric controls (n=323) were compared retrospectively on risk factors, symptom onset, and diagnostic migration. Eating disorder groups reported greater risk exposure than non-psychiatric controls. AN and BED differed on premorbid personality/behavioral problems, childhood obesity, and family overeating. Risk factors for BN were shared with AN and BED. Dieting was the most common onset symptom in AN, whereas binge eating was most common in BN and BED. Migration between AN and BED was rare, but more frequent between AN and BN and between BN and BED. AN and BED have distinct risk factors and onset patterns, while BN shares similar risk factors and onset patterns with both AN and BED. Results should inform future classification schemes and prevention programs. PMID:25103674

  11. The role of insulin in the vascular contributions to age-related dementia.

    PubMed

    Hughes, Timothy M; Craft, Suzanne

    2016-05-01

    In addition to its well-known role in energy metabolism in the body, insulin is a vasoactive hormone that regulates peripheral and cerebral blood flow and neuronal function. Vascular and metabolic dysfunctions are emerging risk factors for Alzheimer's disease (AD) and age-related dementias, and recent evidence suggests that the two pathways are constitutive and interrelated. As a result, an emphasis on correcting metabolic disorders is emerging as an important strategy in the treatment and prevention of age-related cognitive impairment and AD. We review the evidence regarding the unique and interactive effects of vascular and metabolic disorders in pathological brain aging, with special consideration of the role of insulin dysregulation in promoting AD pathologic processes and vascular brain injury. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26657615

  12. Impact of age-related neuroglial cell responses on hippocampal deterioration

    PubMed Central

    Ojo, Joseph O.; Rezaie, Payam; Gabbott, Paul L.; Stewart, Michael G.

    2015-01-01

    Aging is one of the greatest risk factors for the development of sporadic age-related neurodegenerative diseases and neuroinflammation is a common feature of this disease phenotype. In the immunoprivileged brain, neuroglial cells, which mediate neuroinflammatory responses, are influenced by the physiological factors in the microenvironment of the central nervous system (CNS). These physiological factors include but are not limited to cell-to-cell communication involving cell adhesion molecules, neuronal electrical activity and neurotransmitter and neuromodulator action. However, despite this dynamic control of neuroglial activity, in the healthy aged brain there is an alteration in the underlying neuroinflammatory response notably seen in the hippocampus, typified by astrocyte/microglia activation and increased pro-inflammatory cytokine production and signaling. These changes may occur without any overt concurrent pathology, however, they typically correlate with deteriorations in hippocamapal or cognitive function. In this review we examine two important phenomenons, firstly the relationship between age-related brain deterioration (focusing on hippocampal function) and underlying neuroglial response(s), and secondly how the latter affects molecular and cellular processes within the hippocampus that makes it vulnerable to age-related cognitive decline. PMID:25972808

  13. Cholesterol synthesis is the trigger and isoprenoid dependent interleukin-6 mediated inflammation is the common causative factor and therapeutic target for atherosclerotic vascular disease and age-related disorders including osteoporosis and type 2 diabetes.

    PubMed

    Omoigui, Sota

    2005-01-01

    This is a unifying theory that cholesterol metabolites (isoprenoids) are an integral component of the signaling pathway for interleukin-6 (IL-6) mediated inflammation. IL-6 inflammation is the common causative origin for atherosclerosis, peripheral vascular disease, coronary artery disease, and age-related disorders including osteoporosis, dementia, Alzheimer's disease and type 2 diabetes. Therapeutic effects of bisphosphonates and statins are mediated by isoprenoid depletion. Statins and bisphosphonates act in the cholesterol pathway to deplete isoprenoids. Anti-inflammatory properties of statins and bisphosphonates are due to isoprenoid depletion with subsequent inhibition of IL-6 mediated inflammation. Therapeutic targets for the prevention and control of all the above diseases should focus on cholesterol metabolites and IL-6 mediated inflammation. Prevention of atherosclerotic vascular disease and age-related disorders will be by utilization of cholesterol lowering agents or techniques and/or treatment with statins and/or bisphosphonates to inhibit IL-6 inflammation through regulation of cholesterol metabolism. PMID:15935563

  14. Seismic Risk Perception compared with seismic Risk Factors

    NASA Astrophysics Data System (ADS)

    Crescimbene, Massimo; La Longa, Federica; Pessina, Vera; Pino, Nicola Alessandro; Peruzza, Laura

    2016-04-01

    The communication of natural hazards and their consequences is one of the more relevant ethical issues faced by scientists. In the last years, social studies have provided evidence that risk communication is strongly influenced by the risk perception of people. In order to develop effective information and risk communication strategies, the perception of risks and the influencing factors should be known. A theory that offers an integrative approach to understanding and explaining risk perception is still missing. To explain risk perception, it is necessary to consider several perspectives: social, psychological and cultural perspectives and their interactions. This paper presents the results of the CATI survey on seismic risk perception in Italy, conducted by INGV researchers on funding by the DPC. We built a questionnaire to assess seismic risk perception, with a particular attention to compare hazard, vulnerability and exposure perception with the real data of the same factors. The Seismic Risk Perception Questionnaire (SRP-Q) is designed by semantic differential method, using opposite terms on a Likert scale to seven points. The questionnaire allows to obtain the scores of five risk indicators: Hazard, Exposure, Vulnerability, People and Community, Earthquake Phenomenon. The questionnaire was administered by telephone interview (C.A.T.I.) on a statistical sample at national level of over 4,000 people, in the period January -February 2015. Results show that risk perception seems be underestimated for all indicators considered. In particular scores of seismic Vulnerability factor are extremely low compared with house information data of the respondents. Other data collected by the questionnaire regard Earthquake information level, Sources of information, Earthquake occurrence with respect to other natural hazards, participation at risk reduction activities and level of involvement. Research on risk perception aims to aid risk analysis and policy-making by

  15. Angiofluorographic aspects in age-related macular degeneration

    PubMed Central

    Tomi, A; Marin, I

    2014-01-01

    Although AMD (age-related macular degeneration) has been described for over 100 years, there is neither a standard agreement on the definition of specific lesions nor a generally accepted classification system. For example, the age limits for AMD varied widely in different clinical studies; the methods used for examination also vary (visual acuity, perimetry, contrast sensitivity, slit lamp examination of the fundus, retinal photography, fluorescein angiography, indocyanine green angiography). We described the multitude of angiofluorographic aspects in patients with AMD and conceived a classification to be easily used in clinical practice. Although a detailed ophthalmoscopy can often identify the characteristic lesions of AMD, a complete picture is obtained by fluorescein angiography. The angiographic classification of AMD is structured similarly to the clinical one. It has two main patterns, non-exudative and exudative lesions, but it provides more information about the nature of the lesions. In the last three decades, an impressive amount of information regarding the prevalence, progression and risk factors for AMD has been published. The source of this information is mainly represented by the large population studies that are often multicenter studies. Recognizing the clinical signs of AMD and classifying them into different stages is important for the prognosis and the therapeutical decision, but also for conceiving study protocols. PMID:27057244

  16. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer’s Disease

    PubMed Central

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer’s Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer’s Disease. PMID:26937969

  17. Vehicle emission unit risk factors for transportation risk assessments

    SciTech Connect

    Biwer, B.M.; Butler, J.P.

    1999-12-01

    When the transportation risk posed by shipments of hazardous chemical and radioactive materials is being assessed, it is necessary to evaluate the risks associated with both vehicle emissions and cargo-related risks. Diesel exhaust and fugitive dust emissions from vehicles transporting hazardous shipments lead to increased air pollution, which increases the risk of latent fatalities in the affected population along the transport route. The estimated risk from these vehicle-related sources can often by as large or larger than the estimated risk associated with the material being transported. In this paper, data from the US Environmental Protection Agency's Motor Vehicle-Related Air Toxics Study are first used to develop latent cancer fatality estimates per kilometer of travel in rural and urban areas for all diesel truck classes. These unit risk factors are based on studies investigating the carcinogenic nature of diesel exhaust. With the same methodology, the current per=kilometer latent fatality risk factor used in transportation risk assessment for heavy diesel trucks in urban areas is revised and the analysis expanded to provide risk factors for rural areas and all diesel truck classes. These latter fatality estimates may include, but are not limited to, cancer fatalities and are based primarily on the most recent epidemiological data available on mortality rates associated with ambient air PM-10 concentrations.

  18. Vehicle emission unit risk factors for transportation risk assessments.

    PubMed

    Biwer, B M; Butler, J P

    1999-12-01

    When the transportation risk posed by shipments of hazardous chemical and radioactive materials is being assessed, it is necessary to evaluate the risks associated with both vehicle emissions and cargo-related risks. Diesel exhaust and fugitive dust emissions from vehicles transporting hazardous shipments lead to increased air pollution, which increases the risk of latent fatalities in the affected population along the transport route. The estimated risk from these vehicle-related sources can often be as large or larger than the estimated risk associated with the material being transported. In this paper, data from the U.S. Environmental Protection Agency's Motor Vehicle-Related Air Toxics Study are first used to develop latent cancer fatality estimates per kilometer of travel in rural and urban areas for all diesel truck classes. These unit risk factors are based on studies investigating the carcinogenic nature of diesel exhaust. With the same methodology, the current per-kilometer latent fatality risk factor used in transportation risk assessments for heavy diesel trucks in urban areas is revised and the analysis expanded to provide risk factors for rural areas and all diesel truck classes. These latter fatality estimates may include, but are not limited to, cancer fatalities and are based primarily on the most recent epidemiological data available on mortality rates associated with ambient air PM-10 concentrations. PMID:10765454

  19. Genetic Insights into Cardiometabolic Risk Factors

    PubMed Central

    Whitfield, John B

    2014-01-01

    Many biochemical traits are recognised as risk factors, which contribute to or predict the development of disease. Only a few are in widespread use, usually to assist with treatment decisions and motivate behavioural change. The greatest effort has gone into evaluation of risk factors for cardiovascular disease and/or diabetes, with substantial overlap as ‘cardiometabolic’ risk. Over the past few years many genome-wide association studies (GWAS) have sought to account for variation in risk factors, with the expectation that identifying relevant polymorphisms would improve our understanding or prediction of disease; others have taken the direct approach of genomic case-control studies for the corresponding diseases. Large GWAS have been published for coronary heart disease and Type 2 diabetes, and also for associated biomarkers or risk factors including body mass index, lipids, C-reactive protein, urate, liver function tests, glucose and insulin. Results are not encouraging for personal risk prediction based on genotyping, mainly because known risk loci only account for a small proportion of risk. Overlap of allelic associations between disease and marker, as found for low density lipoprotein cholesterol and heart disease, supports a causal association, but in other cases genetic studies have cast doubt on accepted risk factors. Some loci show unexpected effects on multiple markers or diseases. An intriguing feature of risk factors is the blurring of categories shown by the correlation between them and the genetic overlap between diseases previously thought of as distinct. GWAS can provide insight into relationships between risk factors, biomarkers and diseases, with potential for new approaches to disease classification. PMID:24659834

  20. Age-Related Hyperkyphosis: Its Causes, Consequences, and Management

    PubMed Central

    Katzman, Wendy B.; Wanek, Linda; Shepherd, John A.; Sellmeyer, Deborah E.

    2010-01-01

    Age-related postural hyperkyphosis is an exaggerated anterior curvature of the thoracic spine, sometimes referred to as Dowager’s hump or gibbous deformity. This condition impairs mobility,2,31 and increases the risk of falls33 and fractures.26 The natural history of hyperkyphosis is not firmly established. Hyperkyphosis may develop from either muscle weakness and degenerative disc disease, leading to vertebral fractures and worsening hyperkyphosis, or from initial vertebral fractures that precipitate its development. PMID:20511692

  1. Sudden cardiac death: epidemiology and risk factors

    PubMed Central

    Adabag, A. Selcuk; Luepker, Russell V.; Roger, Véronique L.; Gersh, Bernard J.

    2016-01-01

    Sudden cardiac death (SCD) is an important public-health problem with multiple etiologies, risk factors, and changing temporal trends. Substantial progress has been made over the past few decades in identifying markers that confer increased SCD risk at the population level. However, the quest for predicting the high-risk individual who could be a candidate for an implantable cardioverter-defibrillator, or other therapy, continues. In this article, we review the incidence, temporal trends, and triggers of SCD, and its demographic, clinical, and genetic risk factors. We also discuss the available evidence supporting the use of public-access defibrillators. PMID:20142817

  2. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  3. Risk Factors and Levels of Risk for High School Dropouts

    ERIC Educational Resources Information Center

    Suh, Suhyun; Suh, Jingyo

    2007-01-01

    The study in this article identifies three major risk categories of high school dropouts and evaluates the impact of possible prevention strategies. As students accumulate these risks, they became more likely to drop out and prevention programs become less effective. Additionally, it was found that factors influencing the decision to drop out vary…

  4. Risk Factors for Complications of Traumatic Injuries.

    PubMed

    de Aguiar Júnior, Wagner; Saleh, Carmen Mohamad Rida; Whitaker, Iveth Yamaguchi

    2016-01-01

    Complications in hospitalized trauma patients are major causes of morbidity and mortality. The aims of this study were to identify the in-hospital trauma patients' complications and identify the risk factors for complications in this population. A retrospective analysis was conducted in a sample from a Brazilian hospital. The sample consisted of 407 patients, 194 (47.66%) of whom had records of complications. The most common complications were infections (41.80%). The risk factors related to the complications were age, length of hospital stay, external causes, and injury severity. The complications were frequent in this sample, and the risk for complications was characterized by multiple factors. PMID:27618375

  5. Oxidative stress, innate immunity, and age-related macular degeneration

    PubMed Central

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  6. Age-related changes in glial cells of dopamine midbrain subregions in rhesus monkeys

    PubMed Central

    Kanaan, Nicholas M.; Kordower, Jeffrey H.; Collier, Timothy J.

    2010-01-01

    Aging remains the strongest risk factor for developing Parkinson’s disease (PD), and there is selective vulnerability in midbrain DA neuron degeneration in PD. By tracking normal aging-related changes with an emphasis on regional specificity, factors involved in selective vulnerability and resistance to degeneration can be studied. Towards this end, we sought to determine whether age-related changes in microglia and astrocytes in rhesus monkeys are region-specific, suggestive of involvement in regional differences in vulnerability to degeneration that may be relevant to PD pathogenesis. Gliosis in midbrain DA subregions was measured by estimating glia number using unbiased stereology, assessing fluorescence intensity for proteins upregulated during activation, and rating morphology. With normal aging, microglia exhibited increased staining intensity and a shift to more activated morphologies preferentially in the vulnerable substantia nigra-ventral tier (vtSN). Astrocytes did not exhibit age-related changes consistent with an involvement in regional vulnerability in any measure. Our results suggest advancing age is associated with chronic mild inflammation in the vtSN, which may render these DA neurons more vulnerable to degeneration. PMID:18715678

  7. [Research progress on the risk factors of geographic tongue].

    PubMed

    Huamei, Yang; Yu, Zhou; Xin, Zeng; Ga, Liao; Qianming, Chen

    2015-02-01

    Geographic tongue, also called benign migratory glossitis, is a common and superficial benign inflammatory disorder that affects the tongue epithelium. The majority of geographic tongue lesions typically manifest as irregular central erythematous patches. These lesions, which are caused by the loss of filiform papillae, are defined by an elevated whitish band-like border that can change location, size, and pattern over a period of time. Histological observations of the oral mucosa affected by geographic tongue revealed nonspecific inflammation. Some reports described cases of migratory stomatitis, wherein lesions simultaneously manifested on the extra lingual oral mucosa. This condition is also called ectopic geographic tongue, which is clinically and histologically similar to the type normally confined to the tongue. In most cases, patients are asymptomatic and do not require treatment. The condition may spontaneously exhibit periods of remission and exacerbation with good prognosis. The specific etiology of geographic tongue remains unknown. Geographic tongue is age-related and is prevalent among young individuals. Various etiological factors that have been suggested in literature include immunological factors, genetic factors, atopic or allergic tendency, emotional stress, tobacco consumption, hormonal disturbances, and zinc deficiency. Geographic tongue may coexist with other disorders, such as fissured tongue, psoriasis, diabetes mellitus, gastroin- testinal diseases, burning mouth syndrome, and Down syndrome. Experts currently disagree on whether geographic tongue is an oral manifestation of psoriasis. Moreover, some scholars suggest that geographic tongue is a prestage of fissured tongue. The objective of this review is to summarize current research on risk factors of geographic tongue. PMID:25872308

  8. Risk Factors in Adolescent Hypertension.

    PubMed

    Ewald, D Rose; Haldeman PhD, Lauren A

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  9. Risk Factors in Adolescent Hypertension

    PubMed Central

    Ewald, D. Rose; Haldeman, Lauren A.

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  10. Cardiovascular risk factor investigation: a pediatric issue

    PubMed Central

    Rodrigues, Anabel N; Abreu, Glaucia R; Resende, Rogério S; Goncalves, Washington LS; Gouvea, Sonia Alves

    2013-01-01

    Objectives To correlate cardiovascular risk factors (e.g., hypertension, obesity, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, sedentariness) in childhood and adolescence with the occurrence of cardiovascular disease. Sources A systematic review of books and selected articles from PubMed, SciELO and Cochrane from 1992 to 2012. Summary of findings Risk factors for atherosclerosis are present in childhood, although cardiovascular disease arises during adulthood. This article presents the main studies that describe the importance of investigating the risk factors for cardiovascular diseases in childhood and their associations. Significant rates of hypertension, obesity, dyslipidemia, and sedentariness occur in children and adolescents. Blood pressure needs to be measured in childhood. An increase in arterial blood pressure in young people predicts hypertension in adulthood. The death rate from cardiovascular disease is lowest in children with lower cholesterol levels and in individuals who exercise regularly. In addition, there is a high prevalence of sedentariness in children and adolescents. Conclusions Studies involving the analysis of cardiovascular risk factors should always report the prevalence of these factors and their correlations during childhood because these factors are indispensable for identifying an at-risk population. The identification of risk factors in asymptomatic children could contribute to a decrease in cardiovascular disease, preventing such diseases as hypertension, obesity, and dyslipidemia from becoming the epidemics of this century. PMID:23515212

  11. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  12. [Midwives' perception of reproductive risk factors].

    PubMed

    García-Barrios, C; Castañeda-Camey, X; Romero-Guerrero, X; González-Hernández, D; Langer-Glas, A

    1993-01-01

    Midwives in rural areas of the State of Morelos are one of the most important resources used by rural women for health care of pregnancy, delivery and the puerperium. This work was aimed at identifying midwives perceptions of pregnant women's risk factors, in order to include this knowledge in reproductive health programs which articulate institutional and traditional health systems. We applied a questionnaire to all midwives in the Municipalities of Ocuituco, yecapixtla and Zacualpan, Morelos (n = 35). Four key informants were selected and interviewed. These instruments enabled us to measure variability in perception of risk factors. Knowledge of risk factors is defective among midwives. Previous training made a big difference. Sixty three per cent of midwives who attended training courses are better qualified from an academic medicine point of view. Only 28.7 per cent of non-trained midwives (43% for both groups), indicating that sociocultural aspects prevail over technical training in midwives perceptions of reproductive risk factors. PMID:8470023

  13. Pneumococcal Disease: Risk Factors and Transmission

    MedlinePlus

    ... Foundation for Infectious Diseases Sepsis Risk Factors and Transmission Recommend on Facebook Tweet Share Compartir On this ... the brain and spinal cord) Who smoke cigarettes Transmission Pneumococcal bacteria spread from person-to-person by ...

  14. Heart Risk Factors Rise Before Menopause

    MedlinePlus

    ... an associate professor of pediatric endocrinology at the University of Virginia. In the past, he said, experts believed that a rapid increase in heart disease and stroke risk factors took place in women after menopause. They thought ...

  15. Psychosocial Factors in Diabetes and Cardiovascular Risk.

    PubMed

    Hackett, Ruth A; Steptoe, Andrew

    2016-10-01

    Type 2 diabetes is a chronic disease that is increasing in prevalence globally. Cardiovascular disease is a major cause of mortality and morbidity in diabetes, and lifestyle and clinical risk factors do not fully account for the link between the conditions. This article provides an overview of the evidence concerning the role of psychosocial stress factors in diabetes risk, as well as in cardiovascular complications in people with existing diabetes. Several types of psychosocial factors are discussed including depression, other types of emotional distress, exposure to stressful conditions, and personality traits. The potential behavioral and biological pathways linking psychosocial factors to diabetes are presented and implications for patient care are highlighted. PMID:27566328

  16. Osteoporosis Risk Factors in Eighth Grade Students.

    ERIC Educational Resources Information Center

    Lysen, Victoria C.; Walker, Robert

    1997-01-01

    Presents findings from food frequency questionnaires and surveys of 138 Midwestern eighth-grade student-parent pairs. The study examined the incidence of modifiable and nonmodifiable osteoporosis risk factors and compared gender differences. Data analysis indicated that many adolescents possessed several modifiable and nonmodifiable risk factors…

  17. Major Risk Factors for Heart Disease: Diabetes

    MedlinePlus

    ... of people who have diabetes die of some type of cardiovascular disease. Diabetic women are at especially high risk for dying ... aware of my risk factors, such as being diabetic and having a family history of heart ... levels—you are more likely to develop type 2 diabetes. But you can take steps to ...

  18. Childhood myopia: epidemiology, risk factors, and prevention.

    PubMed

    Recko, Matthew; Stahl, Erin Durrie

    2015-01-01

    Our understanding of the dynamic interaction between the eye's growth and its ability to adapt to maintain vision has shown that childhood myopia is a significant prediction of progressive myopia and the potentially severe ocular comorbidities associated with it. It is important for us to better understand this process and its risk factors in order to better develop a prevention and treatment strategy. This article will discuss the epidemiology, risk factors and current therapeutic regimens for reducing myopic progression. PMID:25958656

  19. Cancer associated thrombosis: risk factors and outcomes.

    PubMed

    Eichinger, Sabine

    2016-04-01

    Deep vein thrombosis of the leg and pulmonary embolism are frequent diseases and cancer is one of their most important risk factors. Patients with cancer also have a higher prevalence of venous thrombosis located in other parts than in the legs and/or in unusual sites including upper extremity, splanchnic or cerebral veins. Cancer also affects the risk of arterial thrombotic events particularly in patients with myeloproliferative neoplasms and in vascular endothelial growth factor receptor inhibitor recipients. Several risk factors need to interact to trigger thrombosis. In addition to common risk factors such as surgery, hospitalisation, infection and genetic coagulation disorders, the thrombotic risk is also driven and modified by cancer-specific factors including type, histology, and stage of the malignancy, cancer treatment and certain biomarkers. A venous thrombotic event in a cancer patient has serious consequences as the risk of recurrent thrombosis, the risk of bleeding during anticoagulation and hospitalisation rates are all increased. Survival of cancer patients with thrombosis is worse compared to that of cancer patients without thrombosis, and thrombosis is a leading direct cause of death in cancer patients. PMID:27067965

  20. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    PubMed

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  1. Risk Factors for Homelessness Among US Veterans

    PubMed Central

    Tsai, Jack; Rosenheck, Robert A.

    2015-01-01

    Homelessness among US veterans has been a focus of research for over 3 decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this is the first systematic review to summarize research on risk factors for homelessness among US veterans and to evaluate the evidence for these risk factors. Thirty-one studies published from 1987 to 2014 were divided into 3 categories: more rigorous studies, less rigorous studies, and studies comparing homeless veterans with homeless nonveterans. The strongest and most consistent risk factors were substance use disorders and mental illness, followed by low income and other income-related factors. There was some evidence that social isolation, adverse childhood experiences, and past incarceration were also important risk factors. Veterans, especially those who served since the advent of the all-volunteer force, were at greater risk for homelessness than other adults. Homeless veterans were generally older, better educated, and more likely to be male, married/have been married, and to have health insurance coverage than other homeless adults. More studies simultaneously addressing premilitary, military, and postmilitary risk factors for veteran homelessness are needed. This review identifies substance use disorders, mental illness, and low income as targets for policies and programs in efforts to end homelessness among veterans. PMID:25595171

  2. Risk factors predisposing to congenital heart defects

    PubMed Central

    Ul Haq, Faheem; Jalil, Fatima; Hashmi, Saman; Jumani, Maliha Iqbal; Imdad, Aamer; Jabeen, Mehnaz; Hashmi, Javad Tauseef; Irfan, Furqan Bin; Imran, Muhammad; Atiq, Mehnaz

    2011-01-01

    Introduction: Congenital heart disease (CHD) is associated with multiple risk factors, consanguinity may be one such significant factor. The role of consanguinity in the etiology of CHD is supported by inbreeding studies, which demonstrate an autosomal recessive pattern of inheritance of some congenital heart defects. This study was done to find out the risk factors for CHD. Methods: A case-control study was done on pediatric patients at a tertiary care hospital, Aga Khan University Hospital, located in Karachi, Pakistan. A total of 500 patients, 250 cases and 250 controls were included in the study. Results: Amongst the 250 cases (i.e. those diagnosed with CHD), 122 patients (48.8%) were born of consanguineous marriages while in the controls (i.e. non-CHD) only 72 patients (28.9%) showed a consanguinity amongst parents. On multivariate analysis, consanguinity emerged as an independent risk factor for CHD; adjusted odds ratio 2.59 (95% C. I. 1.73 - 3.87). Other risk factors included low birth weight, maternal co-morbidities, family history of CHD and first born child. On the other hand, medications used by the mother during the index pregnancy, maternal age and gender of the child did not significantly increase the risk of developing CHD. Conclusions: Analyses of our results show that parental consanguinity, family history of CHD, maternal co-morbidities, first born child and low birth weight are independent risk factors for CHD. PMID:21976868

  3. Adolescent Risk Factors for Child Maltreatment

    PubMed Central

    Matsuda, Mauri; Greenman, Sarah J.; Augustyn, Megan Bears; Henry, Kimberly L.; Smith, Carolyn A.; Ireland, Timothy O.

    2014-01-01

    We investigate adolescent risk factors, measured at both early and late adolescence, for involvement in child maltreatment during adulthood. Comprehensive assessments of risk factors for maltreatment that use representative samples with longitudinal data are scarce and can inform multilevel prevention. We use data from the Rochester Youth Development Study, a longitudinal study begun in 1988 with a sample of 1,000 seventh and eighth graders. Participants have been interviewed 14 times and, at the last assessment (age 31), 80% were retained. Risk factors represent 10 developmental domains: area characteristics, family background/structure, parent stressors, exposure to family violence, parent-child relationships, education, peer relationships, adolescent stressors, antisocial behaviors, and precocious transitions to adulthood. Maltreatment is measured by substantiated reports from Child Protective Services records. Many individual risk factors (20 at early adolescence and 14 at later adolescence) are significantly, albeit moderately, predictive of maltreatment. Several developmental domains stand out, including family background/structure, education, antisocial behaviors, and precocious transitions. In addition, there is a pronounced impact of cumulative risk on the likelihood of maltreatment. For example, only 3% of the youth with no risk domains in their background at early adolescence were involved in later maltreatment, but for those with risk in 9 developmental domains the rate was 45%. Prevention programs targeting youth at high risk for engaging in maltreatment should begin during early adolescence when risk factors are already at play. These programs need to be comprehensive, capable of addressing the multiple and interwoven nature of risk that is associated with maltreatment. PMID:24075569

  4. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  5. Ectasia risk factors in refractive surgery

    PubMed Central

    Santhiago, Marcony R; Giacomin, Natalia T; Smadja, David; Bechara, Samir J

    2016-01-01

    This review outlines risk factors of post-laser in situ keratomileusis (LASIK) ectasia that can be detected preoperatively and presents a new metric to be considered in the detection of ectasia risk. Relevant factors in refractive surgery screening include the analysis of intrinsic biomechanical properties (information obtained from corneal topography/tomography and patient’s age), as well as the analysis of alterable biomechanical properties (information obtained from the amount of tissue altered by surgery and the remaining load-bearing tissue). Corneal topography patterns of placido disk seem to play a pivotal role as a surrogate of corneal strength, and abnormal corneal topography remains to be the most important identifiable risk factor for ectasia. Information derived from tomography, such as pachymetric and epithelial maps as well as computational strategies, to help in the detection of keratoconus is additional and relevant. High percentage of tissue altered (PTA) is the most robust risk factor for ectasia after LASIK in patients with normal preoperative corneal topography. Compared to specific residual stromal bed (RSB) or central corneal thickness values, percentage of tissue altered likely provides a more individualized measure of biomechanical alteration because it considers the relationship between thickness, tissue altered through ablation and flap creation, and ultimate RSB thickness. Other recognized risk factors include low RSB, thin cornea, and high myopia. Age is also a very important risk factor and still remains as one of the most overlooked ones. A comprehensive screening approach with the Ectasia Risk Score System, which evaluates multiple risk factors simultaneously, is also a helpful tool in the screening strategy. PMID:27143849

  6. Ectasia risk factors in refractive surgery.

    PubMed

    Santhiago, Marcony R; Giacomin, Natalia T; Smadja, David; Bechara, Samir J

    2016-01-01

    This review outlines risk factors of post-laser in situ keratomileusis (LASIK) ectasia that can be detected preoperatively and presents a new metric to be considered in the detection of ectasia risk. Relevant factors in refractive surgery screening include the analysis of intrinsic biomechanical properties (information obtained from corneal topography/tomography and patient's age), as well as the analysis of alterable biomechanical properties (information obtained from the amount of tissue altered by surgery and the remaining load-bearing tissue). Corneal topography patterns of placido disk seem to play a pivotal role as a surrogate of corneal strength, and abnormal corneal topography remains to be the most important identifiable risk factor for ectasia. Information derived from tomography, such as pachymetric and epithelial maps as well as computational strategies, to help in the detection of keratoconus is additional and relevant. High percentage of tissue altered (PTA) is the most robust risk factor for ectasia after LASIK in patients with normal preoperative corneal topography. Compared to specific residual stromal bed (RSB) or central corneal thickness values, percentage of tissue altered likely provides a more individualized measure of biomechanical alteration because it considers the relationship between thickness, tissue altered through ablation and flap creation, and ultimate RSB thickness. Other recognized risk factors include low RSB, thin cornea, and high myopia. Age is also a very important risk factor and still remains as one of the most overlooked ones. A comprehensive screening approach with the Ectasia Risk Score System, which evaluates multiple risk factors simultaneously, is also a helpful tool in the screening strategy. PMID:27143849

  7. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    PubMed

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system. PMID:26915078

  8. [Epidemiology and risk factors in legionellosis].

    PubMed

    Povová, J; Zlámalová, R; Hozák, A; Martinková, I; Matějková, M; Janout, V

    2014-11-01

    Legionella was discovered in the first half of the 20th century. The main representative of the genus is the bacterial species Legionella pneumophila. Legionella can cause a mild disease with fever but also severe to fatal pneumonia. At highest risk are individuals with an underlying disease, immunosuppressed patients or individuals exposed to other risk factors (e.g. users of addictive substances). Information on the etiology and epidemiology of legionellosis is presented. Selected risk factors are described as well as preventive measures to be taken in water supply and cooling systems. In conclusion, emphasis is placed on the prevention. PMID:25523221

  9. Assessing Susceptibility to Age-related Macular Degeneration with Proteomic and Genomic Biomarkers*

    PubMed Central

    Gu, Jiayin; Pauer, Gayle J. T.; Yue, Xiuzhen; Narendra, Umadevi; Sturgill, Gwen M.; Bena, James; Gu, Xiaorong; Peachey, Neal S.; Salomon, Robert G.; Hagstrom, Stephanie A.; Crabb, John W.

    2009-01-01

    Age-related macular degeneration (AMD) is a progressive disease and major cause of severe visual loss. Toward the discovery of tools for early identification of AMD susceptibility, we evaluated the combined predictive capability of proteomic and genomic AMD biomarkers. We quantified plasma carboxyethylpyrrole (CEP) oxidative protein modifications and CEP autoantibodies by ELISA in 916 AMD and 488 control donors. CEP adducts are uniquely generated from oxidation of docosahexaenoate-containing lipids that are abundant in the retina. Mean CEP adduct and autoantibody levels were found to be elevated in AMD plasma by ∼60 and ∼30%, respectively. The odds ratio for both CEP markers elevated was 3-fold greater or more in AMD than in control patients. Genotyping was performed for AMD risk polymorphisms associated with age-related maculopathy susceptibility 2 (ARMS2), high temperature requirement factor A1 (HTRA1), complement factor H, and complement C3, and the risk of AMD was predicted based on genotype alone or in combination with the CEP markers. The AMD risk predicted for those exhibiting elevated CEP markers and risk genotypes was 2–3-fold greater than the risk based on genotype alone. AMD donors carrying the ARMS2 and HTRA1 risk alleles were the most likely to exhibit elevated CEP markers. The results compellingly demonstrate higher mean CEP marker levels in AMD plasma over a broad age range. Receiver operating characteristic curves suggest that CEP markers alone can discriminate between AMD and control plasma donors with ∼76% accuracy and in combination with genomic markers provide up to ∼80% discrimination accuracy. Plasma CEP marker levels were altered slightly by several demographic and health factors that warrant further study. We conclude that CEP plasma biomarkers, particularly in combination with genomic markers, offer a potential early warning system for assessing susceptibility to this blinding, multifactorial disease. PMID:19202148

  10. Mediterranean Diet and Cardiovascular Risk: Beyond Traditional Risk Factors.

    PubMed

    Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Perez-Caballero, Ana I; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

    2016-04-01

    A strict adherence to the Mediterranean Diet (MedDiet) has repeatedly been linked to a low risk of cardiovascular disease in several situations. Initially, the mechanisms considered as possible causes of this were based on the effects of this dietary pattern on the so-called traditional risk factors (especially lipids and blood pressure). However, the high relative reduction in the prevalence of cardiovascular morbidity and mortality were not proportional to the limited findings about regulation of those traditional risk factors. In addition to several studies confirming the above effects, current research on the MedDiet is being focused on defining its effects on non-traditional risk factors, such as endothelial function, inflammation, oxidative stress, or on controlling the conditions which predispose people to cardiovascular events, such as obesity, metabolic syndrome or type 2 diabetes mellitus. In the current article, after briefly reviewing the known effects of the MedDiet on the traditional risk factors, we will mainly focus on reviewing the current evidence about the effects that this dietary pattern exerts on alternative factors, including postprandial lipemia or coagulation, among others, as well as providing a short review on future directions. PMID:25118147

  11. Risk factors and effective management of preeclampsia

    PubMed Central

    English, Fred A; Kenny, Louise C; McCarthy, Fergus P

    2015-01-01

    Preeclampsia, a hypertensive disorder of pregnancy is estimated to complicate 2%–8% of pregnancies and remains a principal cause of maternal and fetal morbidity and mortality. Preeclampsia may present at any gestation but is more commonly encountered in the third trimester. Multiple risk factors have been documented, including: family history, nulliparity, egg donation, diabetes, and obesity. Significant progress has been made in developing tests to predict risk of preeclampsia in pregnancy, but these remain confined to clinical trial settings and center around measuring angiogenic profiles, including placental growth factor or newer tests involving metabolomics. Less progress has been made in developing new treatments and therapeutic targets, and aspirin remains one of the few agents shown to consistently reduce the risk of developing preeclampsia. This review serves to discuss recent advances in risk factor identification, prediction techniques, and management of preeclampsia in antenatal, intrapartum, and postnatal patients. PMID:25767405

  12. Genetic Evidence for Role of Carotenoids in Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS)

    PubMed Central

    Meyers, Kristin J.; Mares, Julie A.; Igo, Robert P.; Truitt, Barbara; Liu, Zhe; Millen, Amy E.; Klein, Michael; Johnson, Elizabeth J.; Engelman, Corinne D.; Karki, Chitra K.; Blodi, Barbara; Gehrs, Karen; Tinker, Lesley; Wallace, Robert; Robinson, Jennifer; LeBlanc, Erin S.; Sarto, Gloria; Bernstein, Paul S.; SanGiovanni, John Paul; Iyengar, Sudha K.

    2014-01-01

    Purpose. We tested variants in genes related to lutein and zeaxanthin status for association with age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Methods. Of 2005 CAREDS participants, 1663 were graded for AMD from fundus photography and genotyped for 424 single nucleotide polymorphisms (SNPs) from 24 candidate genes for carotenoid status. Of 337 AMD cases 91% had early or intermediate AMD. The SNPs were tested individually for association with AMD using logistic regression. A carotenoid-related genetic risk model was built using backward selection and compared to existing AMD risk factors using the area under the receiver operating characteristic curve (AUC). Results. A total of 24 variants from five genes (BCMO1, BCO2, NPCL1L1, ABCG8, and FADS2) not previously related to AMD and four genes related to AMD in previous studies (SCARB1, ABCA1, APOE, and ALDH3A2) were associated independently with AMD, after adjusting for age and ancestry. Variants in all genes (not always the identical SNPs) were associated with lutein and zeaxanthin in serum and/or macula, in this or other samples, except for BCO2 and FADS2. A genetic risk score including nine variants significantly (P = 0.002) discriminated between AMD cases and controls beyond age, smoking, CFH Y402H, and ARMS2 A69S. The odds ratio (95% confidence interval) for AMD among women in the highest versus lowest quintile for the risk score was 3.1 (2.0–4.9). Conclusions. Variants in genes related to lutein and zeaxanthin status were associated with AMD in CAREDS, adding to the body of evidence supporting a protective role of lutein and zeaxanthin in risk of AMD. PMID:24346170

  13. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  14. The relationship of major American dietary patterns to age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  15. Risk factors and burden of osteoarthritis.

    PubMed

    Palazzo, Clémence; Nguyen, Christelle; Lefevre-Colau, Marie-Martine; Rannou, François; Poiraudeau, Serge

    2016-06-01

    Osteoarthritis (OA) is one of the most common joint disorders worldwide. Its prevalence is increasing because of the growing aging of the population in developed and developing countries as well as an increase in risk factors leading to OA, particularly obesity and a sedentary lifestyle. Risk factors of OA can be divided into person-level factors (age, gender, obesity, genetics and diet) and joint-level factors (injury, malalignment and abnormal loading of the joints) that interact in a complex manner. OA is the 11th cause of disability in the world. It is responsible for activity limitations, particularly walking, and affects participation and quality of life. Patients with OA are at greater risk of all-cause mortality, particularly for cardiovascular diseases, than the general population. This excess mortality is closely associated with disability level. Consequently, strategies to reduce burden through primary and secondary prevention programs are increasingly important. PMID:26904959

  16. Cervical artery dissection: emerging risk factors.

    PubMed

    Micheli, S; Paciaroni, M; Corea, F; Agnelli, G; Zampolini, M; Caso, V

    2010-01-01

    Cervical artery dissection (CAD) represents an increasingly recognized cause of stroke and the most common cause of ischemic stroke in young adults. Many factors have been identified in association with CAD such as primary disease of arterial wall (fibrodysplasia) and other non-specific diseases related to CAD like Ehlers Danlos-syndrome IV, Marfan's syndrome, vessel tortuosity. Moreover, an underlying arteriopathy which could be in part genetically determined, has been suspected. The rule of emerging risk factors for CAD such as recent respiratory tract infection, migraine and hyperhomocysteinemia are still a matter of research. Other known risks factors for CAD are major head/neck trauma like chiropractic maneuver, coughing or hyperextension injury associated to car. We examined emerging risks factors for CAD detected in the last years, as CAD pathogenesis is still not completely understood and needs further investigations. PMID:21270941

  17. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    NASA Astrophysics Data System (ADS)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  18. The Age-Related Eye Disease Study (AREDS): Design Implications AREDS Report No. 1

    PubMed Central

    2006-01-01

    The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study. PMID:10588299

  19. Cumulative Lead Exposure and Age-related Hearing Loss: The VA Normative Aging Study

    PubMed Central

    Park, Sung Kyun; Elmarsafawy, Sahar; Mukherjee, Bhramar; Spiro, Avron; Vokonas, Pantel S.; Nie, Huiling; Weisskopf, Marc G.; Schwartz, Joel; Hu, Howard

    2010-01-01

    Although lead has been associated with hearing loss in occupational settings and in children, little epidemiologic research has been conducted on the impact of cumulative lead exposure on age-related hearing loss in the general population. We determined whether bone lead levels, a marker of cumulative lead exposure, are associated with decreased hearing ability in 448 men from the Normative Aging Study, seen between 1962 and 1996 (2,264 total observations). Air conduction hearing thresholds were measured at 0.25 to 8 kHz and pure tone averages (PTA) (mean of 0.5, 1, 2 and 4 kHz) were computed. Tibia and patella lead levels were measured using K x-ray fluorescence between 1991 and 1996. In cross-sectional analyses, after adjusting for potential confounders including occupational noise, patella lead levels were significantly associated with poorer hearing thresholds at 2, 3, 4, 6 and 8 kHz and PTA. The odds of hearing loss significantly increased with patella lead levels. We also found significant positive associations between tibia lead and the rate change in hearing thresholds at 1, 2, and 8 kHz and PTA in longitudinal analyses. Our results suggest that chronic low-level lead exposure may be an important risk factor for age-related hearing loss and reduction of lead exposure could help prevent or delay development of age-related hearing loss. PMID:20638461

  20. Serum Antioxidative Enzymes Levels and Oxidative Stress Products in Age-Related Cataract Patients

    PubMed Central

    Chang, Dong; Zhang, Xuefei; Rong, Shengzhong; Sha, Qian; Liu, Peipei; Han, Tao; Pan, Hongzhi

    2013-01-01

    Purpose. To investigate the activity of antioxidative enzymes and the products of oxidative stress in patients with age-related cataracts and compare the findings with those in healthy control subjects. Method. Sixty patients with age-related cataract and sixty healthy controls of matched age and gender were included in this study. Serum samples were obtained to detect the antioxidative enzymes of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and oxidation degradation products of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), conjugated diene (CD), advanced oxidation protein products (AOPP), protein carbonyl (PC), and 8-hydroxydeoxyguanosine (8-OHdG). Results. Serum SOD, GSH-Px, and CAT activities in cataract group were significantly decreased as compared to the control subjects (P < 0.05). The levels of MDA, 4-HNE, and CD in cataract patients were significantly higher than those in the control subjects (P < 0.05, P < 0.01). Cataract patients had higher levels of 8-OHdG, AOPP, and PC with respect to the comparative group of normal subjects (P < 0.01). And there was no statistical significance in concentration of antioxidative enzymes and oxidative stress products in patients with different subtype cataract. Conclusions. Oxidative stress is an important risk factor in the development of age-related cataract, and augmentation of the antioxidant defence systems may be of benefit to prevent or delay cataractogenesis. PMID:23781296

  1. Tuberculosis: distribution, risk factors, mortality.

    PubMed

    Kochi, A

    1994-10-01

    About a century after Koch's discovery of the TB bacilli the tuberculosis epidemic which had appeared to be under control was again recognized as a major global health threat. The decline in the epidemic in this century had been largely through the improved living standards and, eventually, the availability and use of effective antibiotics. While tuberculosis gradually disappeared from the health agenda in the western world it remained a big killer throughout the century and in 1992 an estimated 2.7 million TB deaths occurred; 30 million will die from TB during the 1990s if current trends are not reversed. The annual number of new cases will increase from 7.5 million estimated in 1990 to more than 10 million in the year 2000. The main factors for this increase are demographic forces, population movements, the HIV epidemic and increasing drug resistance. The impact of the HIV epidemic is already felt in many sub-Saharan African countries and now threatens Asia where almost two-thirds of the world's TB infected population live and where HIV is spreading. Tuberculosis has also reemerged as a major public health problem in industrialized countries due to international migration, the breakdown of health services, including TB services etc. The control of the epidemic can only be through a concerted action to reinstate TB as priority among health concerns, reflected in national and international resources. A coalition of public and private supporters must be mobilized to support the effort to fight the disease. Governments, non-governmental organizations, the business community, refugee organizations, medical institutions, and other UN agencies are invited to join with WHO in this effort. PMID:7713546

  2. Vulvovaginal candidiasis: Epidemiology, microbiology and risk factors.

    PubMed

    Gonçalves, Bruna; Ferreira, Carina; Alves, Carlos Tiago; Henriques, Mariana; Azeredo, Joana; Silva, Sónia

    2016-11-01

    Vulvovaginal candidiasis (VVC) is an infection caused by Candida species that affects millions of women every year. Although Candida albicans is the main cause of VVC, the identification of non-Candida albicans Candida (NCAC) species, especially Candida glabrata, as the cause of this infection, appears to be increasing. The development of VVC is usually attributed to the disturbance of the balance between Candida vaginal colonization and host environment by physiological or nonphysiological changes. Several host-related and behavioral risk factors have been proposed as predisposing factors for VVC. Host-related factors include pregnancy, hormone replacement, uncontrolled diabetes, immunosuppression, antibiotics, glucocorticoids use and genetic predispositions. Behavioral risk factors include use of oral contraceptives, intrauterine device, spermicides and condoms and some habits of hygiene, clothing and sexual practices. Despite a growing list of recognized risk factors, much remains to be elucidated as the role of host versus microorganisms, in inducing VVC and its recurrence. Thus, this review provides information about the current state of knowledge on the risk factors that predispose to VVC, also including a revision of the epidemiology and microbiology of VVC, as well as of Candida virulence factors associated with vaginal pathogenicity. PMID:26690853

  3. Postoperative respiratory morbidity: identification and risk factors.

    PubMed

    Mitchell, C; Garrahy, P; Peake, P

    1982-04-01

    Two hundred consecutive patients admitted for general surgery were studied prospectively to evaluate the contribution of risk factors to postoperative respiratory morbidity (PORM). PORM was expressed both in terms of individual clinical features present on the second postoperative day (when the incidence was greatest), and as an aggregate score incorporating many clinical features. The importance of recognised risk factors, such as previous respiratory disease, cigarette smoking, upper abdominal procedures and the duration of surgery was confirmed, in that these factors were associated with some of the individual clinical features of PORM. The relative importance and independent contribution of these risk factors were assessed by their association with the aggregate score. A naso-gastric tube (NGT) present for 24 hours postoperatively was the factor more associated with PORM. The NGT identified patients at risk more clearly than, and independently of, the next most important factor, upper abdominal surgery. The duration of surgery did not contribute to PORM after the influence of NGT and site of surgery had been considered. Previous respiratory disease predisposed to PORM, and was best identified by, in order of importance, an observed productive cough, a reduced one second forced expiratory volume, and purulent sputum. After the incidence of these factors had been considered, cigarette smoking and a history of a chronic productive cough did not contribute further to PORM. PMID:6952867

  4. Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.

    PubMed

    Ukraintseva, Svetlana; Yashin, Anatoliy; Arbeev, Konstantin; Kulminski, Alexander; Akushevich, Igor; Wu, Deqing; Joshi, Gaurang; Land, Kenneth C; Stallard, Eric

    2016-02-01

    Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention. PMID:26306600

  5. Industrial risk factors for colorectal cancer

    SciTech Connect

    Lashner, B.A.; Epstein, S.S. )

    1990-01-01

    Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. 143 references.

  6. What Are the Risk Factors for Kidney Cancer?

    MedlinePlus

    ... kidney cancer? What are the risk factors for kidney cancer? A risk factor is anything that affects ... not cancer). Other risk factors Family history of kidney cancer People with a strong family history of ...

  7. Endocrine Risk Factors for Cognitive Impairment.

    PubMed

    Moon, Jae Hoon

    2016-06-01

    Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment has expanded from epidemiology to molecular pathogenesis and therapeutic management. This review focuses on the epidemiological evidence for the association between cognitive impairment and several endocrine risk factors, including insulin resistance, dyslipidemia, thyroid dysfunction, vitamin D deficiency, and subclinical atherosclerosis. Researches suggesting possible mechanisms for this association are reviewed. The research investigating modifiable endocrine risk factors for cognitive impairment provides clues for understanding the pathogenesis of cognitive impairment and developing novel treatment modalities. However, so far, interventional studies investigating the beneficial effect of the "modification" of these "modifiable risk factors" on cognitive impairment have reported variable results. Therefore, well-designed, randomized prospective interventional studies are needed. PMID:27118278

  8. Risk Factors for Recurrent Lumbar Disc Herniation

    PubMed Central

    Huang, Weimin; Han, Zhiwei; Liu, Jiang; Yu, Lili; Yu, Xiuchun

    2016-01-01

    Abstract Recurrent lumbar disc herniation (rLDH) is a common complication following primary discectomy. This systematic review aimed to investigate the current evidence on risk factors for rLDH. Cohort or case-control studies addressing risk factors for rLDH were identified by search in Pubmed (Medline), Embase, Web of Science, and Cochrane library from inception to June 2015. Relevant results were pooled to give overall estimates if possible. Heterogeneity among studies was examined and publication bias was also assessed. A total of 17 studies were included in this systematic review. Risk factors that had significant relation with rLDH were smoking (OR 1.99, 95% CI 1.53–2.58), disc protrusion (OR 1.79, 95% CI 1.15–2.79), and diabetes (OR 1.19, 95% CI 1.06–1.32). Gender, BMI, occupational work, level, and side of herniation did not correlate with rLDH significantly. Based on current evidence, smoking, disc protrusion, and diabetes were predictors for rLDH. Patients with these risk factors should be paid more attention for prevention of recurrence after primary surgery. More evidence provided by high-quality observational studies is still needed to further investigate risk factors for rLDH. PMID:26765413

  9. Endocrine Risk Factors for Cognitive Impairment

    PubMed Central

    2016-01-01

    Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment has expanded from epidemiology to molecular pathogenesis and therapeutic management. This review focuses on the epidemiological evidence for the association between cognitive impairment and several endocrine risk factors, including insulin resistance, dyslipidemia, thyroid dysfunction, vitamin D deficiency, and subclinical atherosclerosis. Researches suggesting possible mechanisms for this association are reviewed. The research investigating modifiable endocrine risk factors for cognitive impairment provides clues for understanding the pathogenesis of cognitive impairment and developing novel treatment modalities. However, so far, interventional studies investigating the beneficial effect of the "modification" of these "modifiable risk factors" on cognitive impairment have reported variable results. Therefore, well-designed, randomized prospective interventional studies are needed. PMID:27118278

  10. Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study. This is a multice...

  11. Environmental risk factors for inflammatory bowel disease.

    PubMed

    Molodecky, Natalie A; Kaplan, Gilaad G

    2010-05-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is associated with significant morbidity. The etiology of IBD has been extensively studied during the last several decades; however, causative factors in disease pathology are not yet fully understood. IBD is thought to result from the interaction between genetic and environmental factors that influence the normal intestinal commensal flora to trigger an inappropriate mucosal immune response. Although many IBD susceptibility genes have been discovered, similar advances in defining environmental risk factors have lagged. A number of environmental risk factors have been explored, including smoking, appendectomy, oral contraceptives, diet, breastfeeding, infections/ vaccinations, antibiotics, and childhood hygiene. However, most of these factors have demonstrated inconsistent findings, thus making additional studies necessary to better understand the etiology of IBD. PMID:20567592

  12. Risk factors of cardiac allograft vasculopathy

    PubMed Central

    Szczurek, Wioletta; Gąsior, Mariusz; Zembala, Marian

    2015-01-01

    Despite advances in prevention and treatment of heart transplant rejection, development of cardiac allograft vasculopathy (CAV) remains the leading factor limiting long-term survival of the graft. Cardiac allograft vasculopathy etiopathogenesis is not fully understood, but a significant role is attributed to endothelial cell damage, caused by immunological and non-immunological mechanisms. Immunological factors include the differences between the recipient's and the donor's HLA systems, the presence of alloreactive antibodies and episodes of acute rejection. Among the non-immunological factors the most important are the age of the donor, ischemia-reperfusion injury and cytomegalovirus infection. The classical cardiovascular risk factors (diabetes, hypertension, obesity and hyperlipidemia) are also important. This study presents an up-to-date overview of current knowledge on the vasculopathy etiopathogenesis and the role played by endothelium and inflammatory processes in CAV, and it also investigates the factors which may serve as risk markers of cardiac allograft vasculopathy. PMID:26855649

  13. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists. PMID:27376795

  14. Environmental risk factors for mycosis fungoides.

    PubMed

    Wohl, Yonit; Tur, Ethel

    2007-01-01

    The rising incidence rates of mycosis fungoides (MF) call for an explanation. Thus, environmental and lifestyle factors were speculated to play a role in the development of lymphoproliferative diseases. It is thought that continuous activation of skin T helper lymphocytes leads to malignant transformation of a specific clone. Possible risk factors that have been implicated are occupational chemical exposure, radiation, drugs and infections. The carcinogenic process is probably multifactorial and multistep, combining the genetic predisposition of the individual and his immune status with various exogenous factors. Using advanced and accurate exposure assessment tools, recent epidemiological data indicate that occupational exposure to chemicals, primarily to aromatic halogenated hydrocarbons, is a major risk factor to develop MF in men (odds ratio 4.6), while exposure to pesticides, a subgroup of the aromatic halogenated hydrocarbons, is a risk factor in both genders (odds ratio 6.8 for men and 2.4 for women). Apparently, concomitant infection with Staphylococcus aureus or with Borrelia species and chronic exposure to UVR are minor risk factors for the development of MF. Further assessment of occupational and environmental exposures is essential for the evaluation of their contribution to the etiology of MF. This will allow the application of preventive and surveillance measures along with adjustment of existing health policies. PMID:17641490

  15. Risk Factors for Smoking in Rural Women

    PubMed Central

    Salsberry, Pamela J.; Ferketich, Amy K.; Ahijevych, Karen L.; Hood, Nancy E.; Paskett, Electra D.

    2012-01-01

    Abstract Background This study examined the association between social, demographic, and psychologic factors and smoking status among Appalachian Ohio women. A secondary aim examined whether specific factors could be identified and segmented for future tailored treatment of tobacco dependence. Methods A cross-sectional survey (n=570) obtained information about social, demographic, and psychologic factors and smoking. Logistic regression described associations between these characteristics and smoking status. Chi-square automatic interaction detection (CHAID) analyses identified subgroups at risk for smoking. Results Fifty-two percent never smoked, with 20.5% and 27.5% categorized as former and current smokers, respectively. Women with low adult socioeconomic position (SEP) were more likely to smoke (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.74-5.34) compared to high SEP women. Other factors associated with current smoking included age 31–50 (OR 2.30, 95% CI 1.22-4.33), age 18–30 (OR 3.29, 95% CI 1.72-5.34), Center for Epidemiologic Studies Depression scale (CES-D) score≥16 (OR 1.99, 95% CI 1.31-3.05), and first pregnancy at age<20 (OR 1.74, 95% CI 1.14-2.66). The prevalence of smoking was 50% among those with four or more risk factors compared to 10% for those reporting no risk factors. CHAID analyses identified low adult SEP and depressive symptoms as the combination of risk factors most strongly associated with smoking; 49.3% of women in this subgroup currently smoked. Conclusions Low SEP in adulthood, maternal circumstances, and depressive symptoms are associated with current smoking. Tailored cessation interventions that address these risk factors should be developed and further evaluated in an attempt to reduce disparities in smoking prevalence among this vulnerable group of women. PMID:22360694

  16. Psychological Factors Linked to Risk Perception

    NASA Astrophysics Data System (ADS)

    Armaş, I.; Creãu, R. Z.; Stǎnciugelu, I.

    2012-04-01

    Risks are mental models, which allow people to cope with dangerous phenomena (Renn, 2008; Jasanoff, 1998). The term "risk" refers to the likelihood of an adverse effect resulting from an event. The aim of the present study is to identify the psychological factors that are most predictive of risk perception in relation with age, gender, educational level and socio-economical status. Earthquake hazard was considered, because it is an emerging danger for Bucharest. 80% of the laypeople sample are waiting for this event to happen in the next three years. By integrating all the research data, it was attempted to build a risk profile of the investigated population, which could be used by institutions responsible for earthquake risk mitigation situations in Bucharest. This research appealed to the social learning Rotter (1966), auto-effectiveness Bandura (1977; 1983), and anxiety and stress theories. We used psychological variables that measured stress, personal effectiveness and the belief in personal control. The multi-modal risk perception questionnaire was structured on a 49 items sequence. The sample was composed of 1.376 participants recruited on a voluntary basis. The characteristics of risk (like probability and magnitude, time scales) are perceived differently according to psychological factors that play a role also in biases in people's ability to draw inferences from probabilistic information (like cognitive dissonance). Since the 1970's, it has been argued that those who perceive life's events as being beyond their locus of control (external locus of control) are significantly more anxious and less adapted. In this research, strongest associations and significant differences were obtained between sex, age and income categories with Stress vulnerability factor and the External Locus of Control factor. The profile of the low risk perceiver is that of a young, more educated, male individual with a higher self- efficacy level and an internal locus of control.

  17. Risk factors for developing atopic dermatitis.

    PubMed

    Carson, Charlotte Giwercman

    2013-07-01

    The aim of this thesis was to investigate possible risk factors affecting the development of AD. AD is a frequent disease among children and has a substantial impact on the lives of both the child and its family. A better understanding of the disease would enable better treatment, prevention and information to the families involved. Previous risk factor studies have been hampered by an unsuitable study design and/or difficulties in standardization when diagnosing AD, which limit their conclusions. In paper I, we conducted a traditional cross-sectional analysis testing 40 possible risk factors for developing AD at 3 years of age. Our data suggested a strong heredity of AD and confirmed the risk associated with the non-functional FLG allele mutations after adjustments for confounders. Besides this mother's dermatitis and father's allergic rhinitis were found to increase the risk of AD. Perinatal exposure to dog was the only environmental exposure that significantly reduced the disease manifestation, suggesting other, yet unknown environmental factors affecting the increasing prevalence of AD in children. Length at birth was shown to be inversely associated with the risk of later developing AD. This traditional risk factor analysis led to two borderline significant results: duration of exclusive breastfeeding and mother's alcohol intake during the 3rd trimester. Since these possible two risk factors could neither be rejected nor accepted, we decided to do two in-depth studies, further investigating these, using longitudinal data information and data analysis instead of the traditional cross-sectional approach (paper II & III). In paper II, we investigated the risk of developing AD and wheezy symptoms until age 2 years depending on duration of breastfeeding. We found an increased risk of AD, but a protective effect on wheezy disorders in infancy from exclusive breastfeeding. The effect of exclusive breastfeeding on the risk of development of AD was significant after

  18. Age-related hair pigment loss.

    PubMed

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. PMID:26370651

  19. Risk Factors for Glaucoma Needing More Attention

    PubMed Central

    Coleman, Anne L; Kodjebacheva, Gergana

    2009-01-01

    Glaucoma is defined as a chronic progressive optic neuropathy, for which elevated intraocular pressure (IOP) is the only modifiable risk factor. Emerging research indicates that modifiable factors besides IOP may be associated with the presence of glaucoma. In this review, we discuss the role of modifiable determinants, specifically socioeconomic status, nutritional intake, body mass index and obesity, exercise, smoking, and sleep apnea, in the presence of glaucoma. Preliminary studies suggest that associations may exist between these non-inherent factors and glaucoma although research had significant limitations. The mechanisms of influence are unknown or understudied. Research needs to incorporate the broader behavioral and social factors that may affect glaucoma status. PMID:19816585

  20. Age-related hypoxia in CNS pathology.

    PubMed

    Bădescu, George Mihai; Fîlfan, Mădălina; Ciobanu, Ovidiu; Dumbravă, DănuŢ Adrian; Popa-Wagner, Aurel

    2016-01-01

    Although neuropathological conditions differ in the etiology of the inflammatory response, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment. Moreover, a number of common risk factors such as obesity, hypertension, diabetes and atherosclerosis are increasingly understood to act as "silent contributors" to neuroinflammation and can underlie the development of disorders such as cerebral small vessel disease (cSVD) and subsequent dementia. On the other hand, acute neuroinflammation, such as in response to traumatic or cerebral ischemia, aggravates the acute damage and can lead to a number of pathological such as depression, post-stroke dementia and potentially neurodegeneration. All of those sequelae impair recovery and most of them provide the ground for further cerebrovascular events and a vicious cycle develops. Therefore, understanding the mechanisms associated with vascular dementia, stroke and related complications is of paramount importance in improving current preventive and therapeutic interventions. Likewise, understanding of molecular factors and pathways associated with neuroinflammation will eventually enable the discovery and implementation of new diagnostic and therapeutic strategies indicated in a wide range of neurological conditions. PMID:27151686

  1. Surgical site infection risk factors and risk stratification.

    PubMed

    Florschutz, Anthony V; Fagan, Ryan P; Matar, Wadih Y; Sawyer, Robert G; Berrios-Torres, Sandra I

    2015-04-01

    Preoperative identification of the risk factors for surgical site infection and patient risk stratification are essential for deciding whether surgery is appropriate, educating patients on their individual risk of complications, and managing postoperative expectations. Early identification of these factors is also necessary to help guide both patient medical optimization and perioperative care planning. Several resources are currently available to track and analyze healthcare-associated infections, including the Centers for Disease Control and Prevention's National Healthcare Safety Network. In addition, the Centers for Disease Control and Prevention and the American Academy of Orthopaedic Surgeons are exploring collaborative opportunities for the codevelopment of a hip and/or knee arthroplasty national quality measure for periprosthetic joint infection. PMID:25808971

  2. Chronic kidney disease - pediatric risk factors.

    PubMed

    Tasic, Velibor; Janchevska, Aleksandra; Emini, Nora; Sahpazova, Emilija; Gucev, Zoran; Polenakovic, Momir

    2016-01-01

    The knowledge about the progression of chronic kidney disease is an important issue for every pediatric nephrologist and pediatrician in order to implement appropriate measures to prevent wasting of renal function and the final consequence - end stage renal disease with the need for the dialysis and transplantation. Therefore it is important to know, treat or ameliorate the standard risk factors such as hypertension, proteinuria, anemia, hyperparathyroidism etc. In this review devoted to the World Kidney Day 2016 we will pay attention to the low birth parameters, obesity, hyperuricemia and smoking which emerged as particularly important risk factors for children and adolescent with chronic kidney disease. PMID:27442412

  3. Occupational Asthma: Etiologies and Risk Factors

    PubMed Central

    2011-01-01

    The purpose of this article is to critically review the available evidence pertaining to occupational, environmental, and individual factors that can affect the development of occupational asthma (OA). Increasing evidence suggests that exploration of the intrinsic characteristics of OA-causing agents and associated structure-activity relationships offers promising avenues for quantifying the sensitizing potential of agents that are introduced in the workplace. The intensity of exposure to sensitizing agents has been identified as the most important environmental risk factor for OA and should remain the cornerstone for primary prevention strategies. The role of other environmental co-factors (e.g., non-respiratory routes of exposure and concomitant exposure to cigarette smoke and other pollutants) remains to be further delineated. There is convincing evidence that atopy is an important individual risk factor for OA induced by high-molecular-weight agents. There is some evidence that genetic factors, such as leukocyte antigen class II alleles, are associated with an increased risk of OA; however, the role of genetic susceptibility factors is likely to be obscured by complex gene-environment interactions. OA, as well as asthma in general, is a complex disease that results from multiple interactions between environmental factors and host susceptibilities. Determining these interactions is a crucial step towards implementing optimal prevention policies. PMID:21738881

  4. The Relationship of Cataract and Cataract Extraction to Age-related Macular Degeneration: The Beaver Dam Eye Study

    PubMed Central

    Klein, Barbara E. K.; Howard, Kerri P.; Lee, Kristine E.; Iyengar, Sudha K.; Sivakumaran, Theru A.; Klein, Ronald

    2012-01-01

    Objective To examine the associations of cataract and cataract surgery with early and late age-related macular degeneration (AMD) over a 20-year interval. Design Longitudinal population-based study of age-related eye diseases. Participants: Beaver Dam Eye Study participants. Methods All persons 43-84 years of age were recruited in 1987-1988. Participants were followed up at five year intervals after the baseline examination in 1988-1990. Examinations consisted of ocular examination with lens and fundus photography, medical history, measurements of blood pressure, height, and weight. Values of risk variables were updated, and incidences of early and late AMD were calculated for each 5-year interval. Odds ratios were computed using discrete linear logistic regression modeling with generalized estimating equation methods to account for correlation between the eyes and multiple intervals. Main Outcome Measures AMD. Results After controlling for age and sex, neither cataract nor cataract surgery was associated with increased odds for developing early AMD. Further controlling for high risk gene alleles (CFH and ARMS2) and other possible risk factors did not materially affect the odds ratio (OR). However, cataract surgery was associated with incidence of late AMD (OR 1.93; 95% CI 1.28, 2.90). This OR was not materially altered by further controlling for high risk alleles (CFH Y402H, ARMS2) or for other risk factors. The OR for late AMD was higher for cataract surgery performed 5 or more years prior as compared to less than 5 years prior. Conclusions These data strongly support the past findings of an association of cataract surgery with late AMD independent of other risk factors including high risk genetic status, and suggest the importance of considering these findings when counseling patients regarding cataract surgery. These findings should provide further impetus for the search for measures to prevent or delay the development of age-related cataract. PMID:22578823

  5. Cardiovascular risk factors following renal transplant

    PubMed Central

    Neale, Jill; Smith, Alice C

    2015-01-01

    Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Non-traditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population. PMID:26722646

  6. Cardiovascular Risk Factors in Severely Obese Adolescents

    PubMed Central

    Michalsky, Marc P.; Inge, Thomas H.; Simmons, Mark; Jenkins, Todd M.; Buncher, Ralph; Helmrath, Michael; Brandt, Mary L.; Harmon, Carroll M.; Courcoulas, Anita; Chen, Michael; Horlick, Mary; Daniels, Stephen R.; Urbina, Elaine M.

    2015-01-01

    IMPORTANCE Severe obesity is increasingly common in the adolescent population but, as of yet, very little information exists regarding cardiovascular disease (CVD) risks in this group. OBJECTIVE To assess the baseline prevalence and predictors of CVD risks among severely obese adolescents undergoing weight-loss surgery. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 28, 2007, to December 30, 2011, at the following 5 adolescent weight-loss surgery centers in the United States: Nationwide Children’s Hospital in Columbus, Ohio; Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio; Texas Children’s Hospital in Houston; University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania; and Children’s Hospital of Alabama in Birmingham. Consecutive patients aged 19 years or younger were offered enrollment in a long-term outcome study; the final analysis cohort consisted of 242 participants. MAIN OUTCOMES AND MEASURES This report examined the preoperative prevalence of CVD risk factors (ie, fasting hyperinsulinemia, elevated high-sensitivity C-reactive protein levels, impaired fasting glucose levels, dyslipidemia, elevated blood pressure, and diabetes mellitus) and associations between risk factors and body mass index (calculated as weight in kilograms divided by height in meters squared), age, sex, and race/ethnicity. Preoperative data were collected within 30 days preceding bariatric surgery. RESULTS The mean (SD) age was 17 (1.6) years and median body mass index was 50.5. Cardiovascular disease risk factor prevalence was fasting hyperinsulinemia (74%), elevated high-sensitivity C-reactive protein levels (75%), dyslipidemia (50%), elevated blood pressure (49%), impaired fasting glucose levels (26%), and diabetes mellitus (14%). The risk of impaired fasting glucose levels, elevated blood pressure, and elevated high-sensitivity C-reactive protein levels increased by 15%, 10%, and 6%, respectively, per 5-unit

  7. College Students' Attitudes towards Age-Related Changes in Physical Appearance.

    ERIC Educational Resources Information Center

    Kanter, Allison; Agliata, Daniel; Tantleff-Dunn, Stacey

    The aim of this study was to identify factors associated with young adults' concerns about age related changes in body image and their anticipated impact on psychosocial functioning. One hundred and sixty-seven college students completed the Body Image and Aging Survey, designed to assess age related issues in body image, the Peer Dieting Survey,…

  8. Risk Factors for Rural Residential Fires

    ERIC Educational Resources Information Center

    Allareddy, Veerasathpurush; Peek-Asa, Corinne; Yang, Jingzhen; Zwerling, Craig

    2007-01-01

    Context and Purpose: Rural households report high fire-related mortality and injury rates, but few studies have examined the risk factors for fires. This study aims to identify occupant and household characteristics that are associated with residential fires in a rural cohort. Methods: Of 1,005 households contacted in a single rural county, 691…

  9. Risk Factors for Depression in Early Adolescence

    ERIC Educational Resources Information Center

    MacPhee, Angela R.; Andrews, Jac J. W.

    2006-01-01

    The purpose of this study was to identify salient risk factors for depression in early adolescence from a group of common predictors. The following nine predictors were examined: (1) perceived quality of peer relationships, (2) perceived parental nurturance, (3) perceived parental rejection, (4) self-esteem, (5) body image, (6) pubertal status,…

  10. Adolescent Suicide Risk: Four Psychosocial Factors

    ERIC Educational Resources Information Center

    Rutter, Philip A.; Behrendt, Andrew E.

    2004-01-01

    Suicide is a leading cause of death among adolescents. This study examined the suicidal ideation, behavior, and attempt history of 100 adolescents ages seventeen to nineteen. Four psychosocial factors were found to be important for overall suicide risk: hopelessness, hostility, negative self-concept, and isolation. It is suggested that focusing on…

  11. Risk Factors for Paternal Physical Child Abuse

    ERIC Educational Resources Information Center

    Lee, Shawna J.; Guterman, Neil B.; Lee, Yookyong

    2008-01-01

    Objective: This study uses the developmental-ecological framework to examine a comprehensive set of paternal factors hypothesized to be linked to risk for paternal child abuse (PCA) among a diverse sample of fathers. Attention was given to fathers' marital status and their race/ethnicity (White, African American, and Hispanic). Methods: Interviews…

  12. Risk Factors for Domestic Violence in Curacao

    ERIC Educational Resources Information Center

    van Wijk, N. Ph. L.; de Bruijn, J. G. M.

    2012-01-01

    One out of three people (25% of men, 38% of women) in Curacao have experienced some form of domestic violence at some point in their adult lives. The most significant risk factors for domestic violence in Curacao are the female gender, a young age, low education, and experiencing domestic violence victimization in childhood. Divorce, single…

  13. Risk Factors and Prodromal Eating Pathology

    ERIC Educational Resources Information Center

    Stice, Eric; Ng, Janet; Shaw, Heather

    2010-01-01

    Prospective studies have identified factors that increase risk for eating pathology onset, including perceived pressure for thinness, thin-ideal internalization, body dissatisfaction, dietary restraint, and negative affect. Research also suggests that body dissatisfaction and dietary restraint may constitute prodromal stages of the development of…

  14. Environmental Risk Factors in Hospital Suicide

    ERIC Educational Resources Information Center

    Lieberman, Daniel Z.; Resnik, Harvey L.P.; Holder-Perkins, Vicenzio

    2004-01-01

    Suicide of hospitalized patients is the most common sentinel event reviewed by The Joint Commission on Accreditation of Healthcare Organizations. Shorter lengths of stay, sicker patients, and higher patient to staff ratios challenge the ability of the hospital to maintain safety. Risk factors associated with the physical environment of the…

  15. Infants at Risk: Perinatal and Neonatal Factors.

    ERIC Educational Resources Information Center

    Lipsitt, Lewis P.

    1979-01-01

    Reviews studies of infant behavior and development. Delineates a behavioral hypothesis relating prenatal and neonatal risk factors in infancy to crib death. The mutual dependence of experience and neurostructural development suggests that infancy is a period of critical learning experiences. (Author/RH)

  16. Risk Factors for Smoking Behaviors among Adolescents

    ERIC Educational Resources Information Center

    Chung, Sung Suk; Joung, Kyoung Hwa

    2014-01-01

    Many students in Korea begin to use tobacco and develop a regular smoking habit before they reach adulthood. Yet, little is known about various signs contributing to the transition of the student smoking behaviors. This study used a national sample to explore and compare risk factors for smoking behaviors. Three types of smoking behaviors were…

  17. Distraction can reduce age-related forgetting.

    PubMed

    Biss, Renée K; Ngo, K W Joan; Hasher, Lynn; Campbell, Karen L; Rowe, Gillian

    2013-04-01

    In three experiments, we assessed whether older adults' generally greater tendency to process distracting information can be used to minimize widely reported age-related differences in forgetting. Younger and older adults studied and recalled a list of words on an initial test and again on a surprise test after a 15-min delay. In the middle (Experiments 1a and 2) or at the end (Experiment 3) of the delay, participants completed a 1-back task in which half of the studied words appeared as distractors. Across all experiments, older adults reliably forgot unrepeated words; however, older adults rarely or never forgot the words that had appeared as distractors, whereas younger adults forgot words in both categories. Exposure to distraction may serve as a rehearsal episode for older adults, and thus as a method by which general distractibility may be co-opted to boost memory. PMID:23426890

  18. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  19. [Age-related changes of sensory system].

    PubMed

    Iwamoto, Toshihiko; Hanyu, Haruo; Umahara, Takahiko

    2013-10-01

    Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease. Reduced sense of taste is well-known especially in salty sense, while the changes of sweet, bitter, and sour tastes are different among individuals. Finally, deep sensation of vibration and proprioception is decreased with age as well as superficial sensation (touch, temperature, pain). As a result, impaired sensory system could induce deterioration of the activities of daily living and quality of life in the elderly. PMID:24261198

  20. Macular carotenoids and age-related maculopathy.

    PubMed

    O'Connell, Eamonn; Neelam, Kumari; Nolan, John; Au Eong, Kah-Guan; Beatty, Stephan

    2006-11-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary supplementation with these carotenoids might prevent, delay, or modify the course of ARM. This article discusses the scientific rationale supporting the hypothesis that L and Z are protective against ARM, and presents the recent evidence germane to this theory. PMID:17160199

  1. Age-related macular degeneration: current treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity. PMID:19668560

  2. [Sexual risk factors among European young people].

    PubMed

    Calatrava, María; López-Del Burgo, Cristina; de Irala, Jokin

    2012-05-01

    The sexual transmission of the human immunodeficiency virus (HIV) and other sexually transmitted infections (STI) in Europe are still rising. In order to prioritize STI prevention strategies in Europe, it is important to describe the prevalence of different sexual risk factors for STIs among European young people. We carried out a systematic review of published articles and studies performed by European institutions. A total of 21 articles and 10 studies were identified. The data shows an increase in early sexual initiation and the number of sexual partners. Young people who use condoms inconsistently ranged from 15 to 20%. The observed risk factors are: unawareness about other STIs different from HIV, being in favour of casual sex, wrongly believing that some measures are effective in avoiding HIV, not being aware of the risks from having multiple sexual partners and unawareness about the sexual transmission of HIV. The data suggests the need to improve the information addressed to youth. PMID:22015005

  3. Risk factors associated with lambing traits.

    PubMed

    McHugh, N; Berry, D P; Pabiou, T

    2016-01-01

    The objective of this study was to establish the risk factors associated with both lambing difficulty and lamb mortality in the Irish sheep multibreed population. A total of 135 470 lambing events from 42 675 ewes in 839 Irish crossbred and purebred flocks were available. Risk factors associated with producer-scored ewe lambing difficulty score (scale of one (no difficulty) to four (severe difficulty)) were determined using linear mixed models. Risk factors associated with the logit of the probability of lamb mortality at birth (i.e. binary trait) were determined using generalised estimating equations. For each dependent variable, a series of simple regression models were developed as well as a multiple regression model. In the simple regression models, greater lambing difficulty was associated with quadruplet bearing, younger ewes, of terminal breed origin, lambing in February; for example, first parity ewes experienced greater (P7.0 kg) birth weights, quadruplet born lambs and lambs that experienced a more difficult lambing (predicted probability of death for lambs that required severe and veterinary assistance of 0.15 and 0.32, respectively); lambs from dual-purpose breeds and born to younger ewes were also at greater risk of mortality. In the multiple regression model, the association between ewe parity, age at first lambing, year of lambing and lamb mortality no longer persisted. The trend in solutions of the levels of each fixed effect that remained associated with lamb mortality in the multiple regression model, did not differ from the trends observed in the simple regression models although the differential in relative risk between the different lambing difficulty scores was greater in the multiple regression model. Results from this study show that many common flock- and animal-level factors are associated with both lambing difficulty and lamb mortality and management of different risk category groups (e.g. scanned litter sizes, ewe age groups) can be used

  4. Cardiovascular Risk Factors of Taxi Drivers.

    PubMed

    Elshatarat, Rami Azmi; Burgel, Barbara J

    2016-06-01

    In the United States (U.S.), cardiovascular disease (CVD) is a major leading cause of death. Despite the high mortality rate related to CVD, little is known about CVD risk factors among urban taxi drivers in the U.S. A cross-sectional design was used to identify the predictors of high cardiovascular risk factors among taxi drivers. Convenience sampling method was used to recruit 130 taxi drivers. A structured questionnaire was used to obtain the data. The sample was male (94 %), age mean (45 ± 10.75) years, married (54 %), born outside of the USA (55 %), had some college or below (61.5 %), night drivers (50.8 %), and driving on average 9.7 years and 41 h/week. About 79 % of them were eligible for CVD prevention, and 35.4 % had high CVD risk factors (4-9 risk factors). A CVD high-risk profile had a significant relationship with the subjects who were ≥55 years old; had hypertension, diabetes, or hyperlipidemia; were drinking alcohol ≥2 times/week; and had insufficient physical activity. Subjects who worked as a taxi driver for more than 10 years (OR 4.37; 95 % CI 1.82, 10.50) and had mental exertion from cab driving >5 out of 10 (OR 2.63; 95 % CI 1.05, 6.57) were more likely to have a CVD high-risk profile. As a conclusion, system-level or worksite interventions include offering healthy food at taxi dispatching locations, creating a work culture of frequent walking breaks, and interventions focusing on smoking, physical activity, and weight management. Improving health insurance coverage for this group of workers is recommended. PMID:27151321

  5. Chronic disease risk factors among hotel workers

    PubMed Central

    Gawde, Nilesh Chandrakant; Kurlikar, Prashika R.

    2016-01-01

    Context: Non-communicable diseases have emerged as a global health issue. Role of occupation in pathogenesis of non-communicable diseases has not been explored much especially in the hospitality industry. Aims: Objectives of this study include finding risk factor prevalence among hotel workers and studying relationship between occupational group and chronic disease risk factors chiefly high body mass index. Settings and Design: A cross-sectional study was conducted among non-managerial employees from classified hotels in India. Materials and Methods: The study participants self-administered pre-designed pilot-tested questionnaires. Statistical analysis used: The risk factor prevalence rates were expressed as percentages. Chi-square test was used for bi-variate analysis. Overweight was chosen as ‘outcome’ variable of interest and binary multi-logistic regression analysis was used to identify determinants. Results: The prevalence rates of tobacco use, alcohol use, inadequate physical activity and inadequate intake of fruits and vegetables were 32%, 49%, 24% and 92% respectively among hotel employees. Tobacco use was significantly common among those in food preparation and service, alcohol use among those in food service and security and leisure time physical activity among front office workers. More than two-fifths (42.7%) were overweight. Among the hotel workers, those employed in food preparation and security had higher odds of 1.650 (CI: 1.025 – 2.655) and 3.245 (CI: 1.296 – 8.129) respectively of being overweight. Conclusions: Prevalence of chronic disease risk factors is high among hotel workers. Risk of overweight is significantly high in food preparation and security departments and workplace interventions are necessary to address these risks PMID:27390474

  6. Prenatal and perinatal risk factors of schizophrenia.

    PubMed

    Meli, Giampiero; Ottl, Birgit; Paladini, Angela; Cataldi, Luigi

    2012-12-01

    Schizophrenia could be considered the most severe of all psychiatric disorders. It shows a heterogeneous clinical picture and presents an etiopathogenesis that is not cleared sufficiently. Even if the etiopathogenesis remains a puzzle, there is a scientific consensus that it is an expression of interaction between genotype and environmental factors. In the present article, following a study of literature and the accumulated evidence, the role of prenatal and perinatal factors in the development of schizophrenia will be revised and synthesized. We think that better knowledge of the risk factors could be helpful not only for better comprehension of the pathogenesis but especially to optimize interventions for prevention of the disorder. PMID:22646662

  7. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  8. What Are the Risk Factors for Breast Cancer in Men?

    MedlinePlus

    ... in men? What are the risk factors for breast cancer in men? A risk factor is anything that ... old when they are diagnosed. Family history of breast cancer Breast cancer risk is increased if other members ...

  9. Drug and Alcohol Use -- A Significant Risk Factor for HIV

    MedlinePlus

    ... A Significant Risk Factor for HIV Drug and Alcohol Use - A Significant Risk Factor for HIV Email ... with HIV currently use drugs or binge on alcohol. Many people are unaware that the increased risk ...

  10. Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes.

    PubMed

    Yin, Xiaoyan; Subramanian, Subha; Willinger, Christine M; Chen, George; Juhasz, Peter; Courchesne, Paul; Chen, Brian H; Li, Xiaohang; Hwang, Shih-Jen; Fox, Caroline S; O'Donnell, Christopher J; Muntendam, Pieter; Fuster, Valentin; Bobeldijk-Pastorova, Ivana; Sookoian, Silvia C; Pirola, Carlos J; Gordon, Neal; Adourian, Aram; Larson, Martin G; Levy, Daniel

    2016-04-01

    This study tested metabolite associations with risk factors cross-sectionally and with risk factor changes over time to uncover mechanistic links between metabolomics dysregulation and metabolic risk. PMID:26908103

  11. What Are the Risk Factors for Ovarian Cancer?

    MedlinePlus

    ... Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor ... in the stomach and intestine while they are teenagers. They also have a high risk of cancer, ...

  12. Risk estimations, risk factors, and genetic variants associated with Alzheimer's disease in selected publications from the Framingham Heart Study.

    PubMed

    Weinstein, Galit; Wolf, Philip A; Beiser, Alexa S; Au, Rhoda; Seshadri, Sudha

    2013-01-01

    The study of Alzheimer's disease (AD) in the Framingham Heart Study (FHS), a multi-generational, community-based population study, began nearly four decades ago. In this overview, we highlight findings from seven prior publications that examined lifetime risk estimates for AD, environmental risk factors for AD, circulating and imaging markers of aging-related brain injury, and explorations on the genetics underlying AD. First, we describe estimations of the lifetime risk of AD. These estimates are distinguished from other measures of disease burden and have substantial public health implications. We then describe prospective studies of environmental AD risk factors: one examined the association between plasma levels of omega-3 fatty-acid and risk of incident AD, the other explored the association of diabetes to this risk in subsamples with specific characteristics. With evidence of inflammation as an underlying mechanism, we also describe findings from a study that compared the effects of serum cytokines and spontaneous production of peripheral blood mononuclear cell cytokines on AD risk. Investigating AD related endophenotypes increases sensitivity in identifying risk factors and can be used to explore pathophysiologic pathways between a risk factor and the disease. We describe findings of an association between large volume of white matter hyperintensities and a specific pattern of cognitive deficits in non-demented participants. Finally, we summarize our findings from two genetic studies: The first used genome-wide association (GWA) and family-based association methods to explore the genetic basis of cognitive and structural brain traits. The second is a large meta-analysis GWA study of AD, in which novel loci of AD susceptibility were found. Together, these findings demonstrate the FHS multi-directional efforts in investigating dementia and AD. PMID:22796871

  13. Review on risk factors of cervical cancer.

    PubMed

    Chou, P

    1991-08-01

    This article reviews risk factors of cervical cancer which have been studied in the following aspects: (1) sociodemographic factors including educational level, urbanizational level, socioeconomic status, race and marriage; (2) sexual activity including age at first marriage, age at first coitus, multiple marriage, multiple sexual partners, broken marriage, unstable sex relationship, syphilis/gonorrhea history, coital frequency, multiple pregnancies and age at menarche; (3) factors related to husband including circumcision, sperm, smegma, previous wife with cervical cancer and occupations entailed mobility of husband and periods away from home; (4) psychosocial factors including stressful emotional status, deprived economic background and discontent home situation; (5) virus including herpes simplex type 2 and papilloma virus; (6) other factors including smoking, barrier and oral contraceptives. PMID:1654190

  14. Factors Affecting Ejection Risk in Rollover Crashes

    PubMed Central

    Funk, James R.; Cormier, Joseph M.; Bain, Charles E.; Wirth, Jeffrey L.; Bonugli, Enrique B.; Watson, Richard A.

    2012-01-01

    Ejection greatly increases the risk of injury and fatality in a rollover crash. The purpose of this study was to determine the crash, vehicle, and occupant characteristics that affect the risk of ejection in rollovers. Information from real world rollover crashes occurring from 2000 – 2010 was obtained from the National Automotive Sampling System (NASS) in order to analyze the effect of the following parameters on ejection risk: seatbelt use, rollover severity, vehicle type, seating position, roof crush, side curtain airbag deployment, glazing type, and occupant age, gender, and size. Seatbelt use was found to reduce the risk of partial ejection and virtually eliminate the risk of complete ejection. For belted occupants, the risk of partial ejection risk was significantly increased in rollover crashes involving more roof inversions, light trucks and vans (LTVs), and larger occupants. For unbelted occupants, the risk of complete ejection was significantly increased in rollover crashes involving more roof inversions, LTVs, far side occupants, and higher levels of roof crush. Roof crush was not a significant predictor of ejection after normalizing for rollover severity. Curtain airbag deployment was associated with reduced rates of partial and complete ejection, but the effect was not statistically significant, perhaps due to the small sample size (n = 89 raw cases with curtain deployments). A much greater proportion of occupants who were ejected in spite of curtain airbag deployment passed through the sunroof and other portals as opposed to the adjacent side window compared to occupants who were ejected in rollovers without a curtain airbag deployment. The primary factors that reduce ejection risk in rollover crashes are, in generally decreasing order of importance: seatbelt use, fewer roof inversions, passenger car body type, curtain airbag deployment, near side seating position, and small occupant size. PMID:23169130

  15. Factors affecting ejection risk in rollover crashes.

    PubMed

    Funk, James R; Cormier, Joseph M; Bain, Charles E; Wirth, Jeffrey L; Bonugli, Enrique B; Watson, Richard A

    2012-01-01

    Ejection greatly increases the risk of injury and fatality in a rollover crash. The purpose of this study was to determine the crash, vehicle, and occupant characteristics that affect the risk of ejection in rollovers. Information from real world rollover crashes occurring from 2000 - 2010 was obtained from the National Automotive Sampling System (NASS) in order to analyze the effect of the following parameters on ejection risk: seatbelt use, rollover severity, vehicle type, seating position, roof crush, side curtain airbag deployment, glazing type, and occupant age, gender, and size. Seatbelt use was found to reduce the risk of partial ejection and virtually eliminate the risk of complete ejection. For belted occupants, the risk of partial ejection risk was significantly increased in rollover crashes involving more roof inversions, light trucks and vans (LTVs), and larger occupants. For unbelted occupants, the risk of complete ejection was significantly increased in rollover crashes involving more roof inversions, LTVs, far side occupants, and higher levels of roof crush. Roof crush was not a significant predictor of ejection after normalizing for rollover severity. Curtain airbag deployment was associated with reduced rates of partial and complete ejection, but the effect was not statistically significant, perhaps due to the small sample size (n = 89 raw cases with curtain deployments). A much greater proportion of occupants who were ejected in spite of curtain airbag deployment passed through the sunroof and other portals as opposed to the adjacent side window compared to occupants who were ejected in rollovers without a curtain airbag deployment. The primary factors that reduce ejection risk in rollover crashes are, in generally decreasing order of importance: seatbelt use, fewer roof inversions, passenger car body type, curtain airbag deployment, near side seating position, and small occupant size. PMID:23169130

  16. Chronic migraine: risk factors, mechanisms and treatment.

    PubMed

    May, Arne; Schulte, Laura H

    2016-08-01

    Chronic migraine has a great detrimental influence on a patient's life, with a severe impact on socioeconomic functioning and quality of life. Chronic migraine affects 1-2% of the general population, and about 8% of patients with migraine; it usually develops from episodic migraine at an annual conversion rate of about 3%. The chronification is reversible: about 26% of patients with chronic migraine go into remission within 2 years of chronification. The most important modifiable risk factors for chronic migraine include overuse of acute migraine medication, ineffective acute treatment, obesity, depression and stressful life events. Moreover, age, female sex and low educational status increase the risk of chronic migraine. The pathophysiology of migraine chronification can be understood as a threshold problem: certain predisposing factors, combined with frequent headache pain, lower the threshold of migraine attacks, thereby increasing the risk of chronic migraine. Treatment options include oral medications, nerve blockade with local anaesthetics or corticoids, and neuromodulation. Well-defined diagnostic criteria are crucial for the identification of chronic migraine. The International Headache Society classification of chronic migraine was recently updated, and now allows co-diagnosis of chronic migraine and medication overuse headache. This Review provides an up-to-date overview of the classification of chronic migraine, basic mechanisms and risk factors of migraine chronification, and the currently established treatment options. PMID:27389092

  17. Psychosocial risk factors for coronary heart disease.

    PubMed

    Glozier, Nick; Tofler, Geoffrey H; Colquhoun, David M; Bunker, Stephen J; Clarke, David M; Hare, David L; Hickie, Ian B; Tatoulis, James; Thompson, David R; Wilson, Alison; Branagan, Maree G

    2013-08-01

    In 2003, the National Heart Foundation of Australia published a position statement on psychosocial risk factors and coronary heart disease (CHD). This consensus statement provides an updated review of the literature on psychosocial stressors, including chronic stressors (in particular, work stress), acute individual stressors and acute population stressors, to guide health professionals based on current evidence. It complements a separate updated statement on depression and CHD. Perceived chronic job strain and shift work are associated with a small absolute increased risk of developing CHD, but there is limited evidence regarding their effect on the prognosis of CHD. Evidence regarding a relationship between CHD and job (in)security, job satisfaction, working hours, effort-reward imbalance and job loss is inconclusive. Expert consensus is that workplace programs aimed at weight loss, exercise and other standard cardiovascular risk factors may have positive outcomes for these risk factors, but no evidence is available regarding the effect of such programs on the development of CHD. Social isolation after myocardial infarction (MI) is associated with an adverse prognosis. Expert consensus is that although measures to reduce social isolation are likely to produce positive psychosocial effects, it is unclear whether this would also improve CHD outcomes. Acute emotional stress may trigger MI or takotsubo ("stress") cardiomyopathy, but the absolute increase in transient risk from an individual stressor is low. Psychosocial stressors have an impact on CHD, but clinical significance and prevention require further study. Awareness of the potential for increased cardiovascular risk among populations exposed to natural disasters and other conditions of extreme stress may be useful for emergency services response planning. Wider public access to defibrillators should be available where large populations gather, such as sporting venues and airports, and as part of the response

  18. The risk factors for labor onset hypertension.

    PubMed

    Ohno, Yasumasa; Terauchi, Mikio; Tamakoshi, Koji; Shiozaki, Arihiro; Saito, Shigeru

    2016-04-01

    Our aim was to clarify the perinatal outcomes of and risk factors for hypertension that is first detected after labor onset (labor onset hypertension, LOH), which may be a risk factor for eclampsia and stroke during labor. A total of 1349 parturient women who did not exhibit preeclampsia or gestational hypertension prior to labor were examined. The patients were classified into four groups: the normotensive (n=1023) (whose systolic blood pressure (SBP) remained below 140 mm Hg throughout labor), mild LOH (n=241) (whose maximum SBP during labor ranged from 140 to 159 mm Hg), severe LOH (n=66) (whose maximum SBP during labor ranged from 160 to 179 mm Hg) and emergent LOH groups (n=19) (whose maximum SBP during labor was greater than 180 mm Hg). The perinatal outcomes and patient characteristics of the four groups were compared. Twenty-four percent of the pregnant women who remained normotensive throughout pregnancy developed hypertension during labor. One of the patients in the emergent LOH group developed eclampsia. The blood pressure at delivery and frequencies of hypotensor use, interventional delivery and low Apgar scores differed significantly among the four groups. The following risk factors for severe/emergent LOH were extracted: being over 35 years old, a body mass index at delivery of >30, an SBP at 36 weeks' gestation of 130-134 mm Hg, an SBP at admission of 130-139 mm Hg, proteinuria (a score of 2+ on the dipstick test) and severe edema. The risk factors for severe/emergent LOH were identified in this study. In high risk cases, repeatedly measuring maternal blood pressure during delivery might help detect critical hypertension early. PMID:26490090

  19. Risk factors for dementia with Lewy bodies

    PubMed Central

    Boot, Brendon P.; Orr, Carolyn F.; Ahlskog, J. Eric; Ferman, Tanis J.; Roberts, Rosebud; Pankratz, Vernon S.; Dickson, Dennis W.; Parisi, Joseph; Aakre, Jeremiah A.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

    2013-01-01

    Objective: To determine the risk factors associated with dementia with Lewy bodies (DLB). Methods: We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort. Results: Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5–16; p < 0.0001), depression (6.0; 3.7–9.5; p < 0.0001), stroke (2.8; 1.3–6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5–8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5–3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27–0.70; p = 0.0006) or use caffeine (0.29; 0.14–0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42–1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3–8.5; p < 0.0001), have a history of depression (4.3; 2.4–7.5; p < 0.0001), be more educated (2.5; 1.1–5.6; p = 0.031), have a positive family history of PD (5.0; 2.4–10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40–0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5–39; p = 0.015). Conclusion: DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either. PMID:23892702

  20. Menopause, obesity and inflammation: interactive risk factors for Alzheimer’s disease

    PubMed Central

    Christensen, Amy; Pike, Christian J.

    2015-01-01

    Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder, the development of which is regulated by several environmental and genetic risk factors. Two factors theorized to contribute to the initiation and/or progression of AD pathogenesis are age-related increases in inflammation and obesity. These factors may be particularly problematic in women. The onset of menopause in mid-life elevates the vulnerability of women to AD, an increased risk that is likely associated with the depletion of estrogens. Menopause is also linked with an abundance of additional changes, including increased central adiposity and inflammation. Here, we review the current literature to explore the interactions between obesity, inflammation, menopause and AD. PMID:26217222

  1. Risk factors for suicidal behavior in adolescents.

    PubMed

    Kirkcaldy, B D; Siefen, G R; Urkin, J; Merrick, J

    2006-10-01

    Adolescent suicide is today a public health problem among the leading cause of mortality among adolescents and young adults. There seems to be many reasons for this increase (which has different trends in different populations), but associations have been found with increased substance abuse, television and video violence, socio-economic status and easy access to firearms. Gender differences have also been observed with crime, suicide and substance abuse higher among males, while eating disorder, depression and suicidal behavior more prevalent among females. This paper will review prevalence and incidence of adolescent suicidal behavior, socio-demographic and psychological risk factors, associated cognitive factors and socio-economic factors. Risk factors include previous suicide attempts, a history of others in the family who have been suicidal, mental illness, alcohol and drug use, and other self-destructive behaviors as well as consideration being given to hopelessness, hostility, negative self-concept and isolation. At the individual difference level, factors such as trait depression, anger and hostility, perfectionism and social sensitivity would seem critical variables, as would age, gender and intellectual functioning. Sociological and family-related factors may also be implicated including dysfunctional family organizations, a history of physical or psychological abuse (sexual abuse) and limited extent of social support networks. A frequently reported precipitating event of suicidal behavior is family adversity including rejection, separation and interpersonal conflict. At a socio-economic level it would seem essential to provide comprehensive document about the social and economic conditions from which the adolescent comes. PMID:17008855

  2. Breast cancer epidemiology and risk factors.

    PubMed

    Broeders, M J; Verbeek, A L

    1997-09-01

    Breast cancer is the most common malignancy among women in the Western society. Over the past decades it has become apparent that breast cancer incidence rates are increasing steadily, whereas the mortality rates for breast cancer have remained relatively constant. Information through the media on this rising number of cases has increased breast health awareness but has also introduced anxiety in the female population. This combination of factors has made the need for prevention of breast cancer an urgent matter. Breast cancer does not seem to be a single disease entity. A specific etiologic factor may therefore have more influence on one form of breast cancer than another. So far though, as shown in our summary of current knowledge on established and dubious risk factors, no risk factors have been identified that can explain a major part of the incidence. Efforts to identify other ways for primary prevention have also been discouraging, even though breast cancer is one of the most investigated tumours world-wide. Thus, at this point in time, the most important strategy to reduce breast cancer mortality is early detection through individual counselling and organised breast screening programs. The recent isolation of breast cancer susceptibility genes may introduce new ways to reduce the risk of breast cancer in a small subset of women. PMID:9274126

  3. Treatment Efficacy and Risk Factors of Neurobrucellosis

    PubMed Central

    Zhao, Shigang; Cheng, Yan; Liao, Yali; Zhang, Zhelin; Yin, Xuhua; Shi, Shujun

    2016-01-01

    Background This study aimed to analyze the risk factors and treatment efficacy of neurobrucellosis. Material/Methods A cross-sectional epidemiologic survey was carried out in 557 patients with brucellosis by specially trained neurologic clinicians. Sixty-six patients with neurobrucellosis were treated with doxycycline, rifampicin, and ceftriaxone sodium as standard medication and evaluated for efficacy on a regular basis. Results (1) Symptoms improved in most patients after 6 weeks of treatment, which demonstrated a favorable efficacy. (2) Cross-sectional epidemiologic survey suggested that sex, nationality, and regional distribution were not related to nervous system damage in patients with brucellosis (P>0.05), whereas age and duration of disease were related factors. Increased age as well as a prolonged duration of disease were risk factors for nervous system damage in patients with brucellosis (P<0.05). Conclusions (1) Doxycycline, rifampicin, and third-generation cephalosporins should be considered both standard and first-choice medications for neurobrucellosis. Treatment should last for at least 6 weeks. Standardized, sufficient, and combined medication is recommended for better efficacy and prognosis. (2) Age and duration of disease are risk factors for neurobrucellosis, whereas sex, nationality, and regional distribution are not. Older patients with a prolonged duration of disease are more likely to develop neurobrucellosis. PMID:27018084

  4. Treatment Efficacy and Risk Factors of Neurobrucellosis.

    PubMed

    Zhao, Shigang; Cheng, Yan; Liao, Yali; Zhang, Zhelin; Yin, Xuhua; Shi, Shujun

    2016-01-01

    BACKGROUND This study aimed to analyze the risk factors and treatment efficacy of neurobrucellosis. MATERIAL AND METHODS A cross-sectional epidemiologic survey was carried out in 557 patients with brucellosis by specially trained neurologic clinicians. Sixty-six patients with neurobrucellosis were treated with doxycycline, rifampicin, and ceftriaxone sodium as standard medication and evaluated for efficacy on a regular basis. RESULTS (1) Symptoms improved in most patients after 6 weeks of treatment, which demonstrated a favorable efficacy. (2) Cross-sectional epidemiologic survey suggested that sex, nationality, and regional distribution were not related to nervous system damage in patients with brucellosis (P>0.05), whereas age and duration of disease were related factors. Increased age as well as a prolonged duration of disease were risk factors for nervous system damage in patients with brucellosis (P<0.05). CONCLUSIONS (1) Doxycycline, rifampicin, and third-generation cephalosporins should be considered both standard and first-choice medications for neurobrucellosis. Treatment should last for at least 6 weeks. Standardized, sufficient, and combined medication is recommended for better efficacy and prognosis. (2) Age and duration of disease are risk factors for neurobrucellosis, whereas sex, nationality, and regional distribution are not. Older patients with a prolonged duration of disease are more likely to develop neurobrucellosis. PMID:27018084

  5. Age-Related Macular Degeneration: Advances in Management and Diagnosis.

    PubMed

    Yonekawa, Yoshihiro; Miller, Joan W; Kim, Ivana K

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  6. Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration

    PubMed Central

    Kang, Eui Chun; Koh, Hyoung Jun

    2015-01-01

    Herein, we review the association between vitreomacular adhesion (VMA) and neovascular age-related macular degeneration (AMD). Meta-analyses have shown that eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in neovascular AMD may induce inflammation, macular traction, decrease in oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other cytokines or may directly stimulate VEGF production. VMA may also interfere with the treatment effects of anti-VEGF therapy, which is the standard treatment for neovascular AMD, and releasing VMA can improve the treatment response to anti-VEGF treatment in neovascular AMD. We also reviewed currently available methods of relieving VMA. PMID:26425354

  7. Age-Related Macular Degeneration: Advances in Management and Diagnosis

    PubMed Central

    Yonekawa, Yoshihiro; Miller, Joan W.; Kim, Ivana K.

    2015-01-01

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in older populations in industrialized nations. AMD is a late-onset deterioration of photoreceptors and retinal pigment epithelium in the central retina caused by various environmental and genetic factors. Great strides in our understanding of AMD pathogenesis have been made in the past several decades, which have translated into revolutionary therapeutic agents in recent years. In this review, we describe the clinical and pathologic features of AMD and present an overview of current diagnosis and treatment strategies. PMID:26239130

  8. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  9. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  10. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  11. Age-related crosslink in skin collagen

    SciTech Connect

    Yamauchi, M.; Mechanic, G.

    1986-05-01

    A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.

  12. Risk factors for depression after a disaster.

    PubMed

    Person, Cheryl; Tracy, Melissa; Galea, Sandro

    2006-09-01

    Environmental stressors such as mass disasters may contribute to an increased prevalence of depression within the population affected. We examined the prevalence of probable major depression and risk factors for depression in the 6-month period after the September 11, 2001, attacks on the World Trade Center among New York City (NYC) metropolitan residents. A total of 2700 persons who were representative of the NYC metropolitan area were included in this cross-sectional telephone survey. The prevalence of probable major depression in the 6 months after the attacks was 9.4%. Multivariate logistic regression covariates associated with the likelihood of probable major depression included being directly affected by the attacks, having a perievent panic attack, experiencing multiple life stressors, and having been exposed to previous traumatic events. Mass traumatic event exposure appears to be an independent environmental risk factor for depression in the postdisaster context; specific reactions such as perievent panic attacks may have prognostic value. PMID:16971817

  13. Bacterial meningitis: a new risk factor

    PubMed Central

    Ataee, Ramezan Ali; Mehrabi-Tavana, Ali; Izadi, Morteza; Hosseini, Sayed Mohammad Javad; Ataee, Mohammad Hossein

    2011-01-01

    BACKGROUND: The purpose of this study is to discuss a possible new risk factor for the bacterial meningitis. METHODS: Cerebrospinal fluid collected from 270 patients was assayed. An enzyme immunosorbent assay for the detection of Staphylococcal enterotoxins A to E was used. RESULTS: The results indicated that the frequency of Coagulase Negative Staphylococci (CoNS) was 35 (20.46%). An important finding of this research was that the CoNS isolates produced enterotoxin C and D or enterotoxin C and E. CONCLUSIONS: This is the first report of enterotoxin-producing Coagulase Negative Staphylococci isolated from CSF patients. Therefore, these enterotoxins probably act as risk factors in the bacterial invasion into central nervous system. PMID:22091233

  14. Trends in major risk factors. Cigarette smoking.

    PubMed Central

    Simpson, D.

    1984-01-01

    The object of this paper is to examine the role of smoking as a risk factor in coronary heart disease, starting with a brief history of smoking in the U.K. and a reminder of the epidemiological evidence linking smoking and cardiovascular disease. This is followed by a more detailed look at the trends in consumption of tobacco and the major factors influencing those trends, together with an outline of the main components of a smoking control policy designed to combat our epidemic of smoking-induced disease. PMID:6694941

  15. Risk factors for amyotrophic lateral sclerosis

    PubMed Central

    Ingre, Caroline; Roos, Per M; Piehl, Fredrik; Kamel, Freya; Fang, Fang

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. It is typically fatal within 2–5 years of symptom onset. The incidence of ALS is largely uniform across most parts of the world, but an increasing ALS incidence during the last decades has been suggested. Although recent genetic studies have substantially improved our understanding of the causes of ALS, especially familial ALS, an important role of non-genetic factors in ALS is recognized and needs further study. In this review, we briefly discuss several major genetic contributors to ALS identified to date, followed by a more focused discussion on the most commonly examined non-genetic risk factors for ALS. We first review factors related to lifestyle choices, including smoking, intake of antioxidants, physical fitness, body mass index, and physical exercise, followed by factors related to occupational and environmental exposures, including electromagnetic fields, metals, pesticides, β-methylamino-L-alanine, and viral infection. Potential links between ALS and other medical conditions, including head trauma, metabolic diseases, cancer, and inflammatory diseases, are also discussed. Finally, we outline several future directions aiming to more efficiently examine the role of non-genetic risk factors in ALS. PMID:25709501

  16. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  17. Risk factors for hypospadias in China

    PubMed Central

    Xu, Ling-Fan; Liang, Chao-Zhao; Lipianskaya, Julia; Chen, Xian-Guo; Fan, Song; Zhang, Li; Zhou, Jun; Tai, Sheng; Jiang, Chang-Qin

    2014-01-01

    This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients (5.1%) were from families with genital anomaly, including five families (2.6%) with hypospadias. The risks of hypospadias was higher for children of mothers > 35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias. PMID:24875823

  18. Engaging Physicians in Risk Factor Reduction

    PubMed Central

    Friedman, Felix; Gumnit, Stephen A.; Schmidt, Eric J.

    2010-01-01

    Abstract OptumHealth tested the feasibility of physician-directed population management in 3 primary care practices and with 546 continuously insured patients who exhibited claims markers for coronary artery disease, diabetes, and/or hypertension. During the intervention portion of the study, we asked physicians to improve the following health measurements: blood pressure, body mass index, cholesterol, hemoglobin A1c, and smoking status. We offered a modest pay-for-outcomes incentive for each risk factor improvement achieved. Additionally, on an eligible subset of these patients, we asked physicians to actively refer to population management programs those patients they determined could benefit from nurse or health coach interventions, advising us as to which components of their treatment plan they wished us to address. The 6-month intervention period exhibited a 10-fold improvement in the trend rate of risk factor management success when compared to the prior 6-month period for the same patients. A net of 96 distinct risk factor improvements were achieved by the 546 patients during the intervention period, whereas 9 net risk factor improvements occurred in the comparison period. This difference in improvement trends was statistically significant at P < 0.01. Of the 546 study participants, a subset of 187 members was eligible for participation in OptumHealth care management programs. Physicians identified 80 of these 187 eligible members as appropriate targets for program intervention. Representing ourselves as “calling on behalf” of the physician practices, we established contact with 50 referred members; 43 members (86%) actively enrolled in our programs. This enrollment rate is 2 to 3 times the rate of enrollment through our standard program outreach methods. We conclude that physician-directed population management with aligned incentives offers promise as a method of achieving important health and wellness goals. (Population Health Management 2010

  19. Engaging physicians in risk factor reduction.

    PubMed

    Springrose, James V; Friedman, Felix; Gumnit, Stephen A; Schmidt, Eric J

    2010-10-01

    OptumHealth tested the feasibility of physician-directed population management in 3 primary care practices and with 546 continuously insured patients who exhibited claims markers for coronary artery disease, diabetes, and/or hypertension. During the intervention portion of the study, we asked physicians to improve the following health measurements: blood pressure, body mass index, cholesterol, hemoglobin A1c, and smoking status. We offered a modest pay-for-outcomes incentive for each risk factor improvement achieved. Additionally, on an eligible subset of these patients, we asked physicians to actively refer to population management programs those patients they determined could benefit from nurse or health coach interventions, advising us as to which components of their treatment plan they wished us to address. The 6-month intervention period exhibited a 10-fold improvement in the trend rate of risk factor management success when compared to the prior 6-month period for the same patients. A net of 96 distinct risk factor improvements were achieved by the 546 patients during the intervention period, whereas 9 net risk factor improvements occurred in the comparison period. This difference in improvement trends was statistically significant at P < 0.01. Of the 546 study participants, a subset of 187 members was eligible for participation in OptumHealth care management programs. Physicians identified 80 of these 187 eligible members as appropriate targets for program intervention. Representing ourselves as "calling on behalf" of the physician practices, we established contact with 50 referred members; 43 members (86%) actively enrolled in our programs. This enrollment rate is 2 to 3 times the rate of enrollment through our standard program outreach methods. We conclude that physician-directed population management with aligned incentives offers promise as a method of achieving important health and wellness goals. PMID:20879906

  20. Risk Factors for Herpes Zoster Among Adults.

    PubMed

    Marin, Mona; Harpaz, Rafael; Zhang, John; Wollan, Peter C; Bialek, Stephanie R; Yawn, Barbara P

    2016-09-01

    Background.  The causes of varicella-zoster virus reactivation and herpes zoster (HZ) are largely unknown. We assessed potential risk factors for HZ, the data for which cannot be obtained from the medical sector. Methods.  We conducted a matched case-control study. We established active surveillance in Olmsted County, Minnesota to identify HZ occurring among persons age ≥50 years during 2010-2011. Cases were confirmed by medical record review. Herpes zoster-free controls were age- and sex-matched to cases. Risk factor data were obtained by telephone interview. Results.  We enrolled 389 HZ case patients and 511 matched controls; the median age was 65 and 66 years, respectively. Herpes zoster was associated with family history of HZ (adjusted odds ratio [aOR] = 1.65); association was highest with first-degree or multiple relatives (aOR = 1.87 and 3.08, respectively). Herpes zoster was also associated with prior HZ episodes (aOR = 1.82), sleep disturbance (aOR = 2.52), depression (aOR = 3.81), and recent weight loss (aOR = 1.95). Stress was a risk factor for HZ (aOR = 2.80), whereas a dose-response relationship was not noted. All associations indicated were statistically significant (P < .05). Herpes zoster was not associated with trauma, smoking, tonsillectomy, diet, or reported exposure to pesticides or herbicides (P > .1). Conclusions.  We identified several important risk factors for HZ; however, the key attributable causes of HZ remain unknown. PMID:27382600

  1. Perinatal Risk Factors for Mild Motor Disability

    ERIC Educational Resources Information Center

    Hands, Beth; Kendall, Garth; Larkin, Dawne; Parker, Helen

    2009-01-01

    The aetiology of mild motor disability (MMD) is a complex issue and as yet is poorly understood. The aim of this study was to identify the prevalence of perinatal risk factors in a cohort of 10-year-old boys and girls with (n = 362) and without (n = 1193) MMD. Among the males with MMD there was a higher prevalence of postpartum haemorrhage,…

  2. Risk Factors for Herpes Zoster Among Adults

    PubMed Central

    Marin, Mona; Harpaz, Rafael; Zhang, John; Wollan, Peter C.; Bialek, Stephanie R.; Yawn, Barbara P.

    2016-01-01

    Background. The causes of varicella-zoster virus reactivation and herpes zoster (HZ) are largely unknown. We assessed potential risk factors for HZ, the data for which cannot be obtained from the medical sector. Methods. We conducted a matched case-control study. We established active surveillance in Olmsted County, Minnesota to identify HZ occurring among persons age ≥50 years during 2010–2011. Cases were confirmed by medical record review. Herpes zoster-free controls were age- and sex-matched to cases. Risk factor data were obtained by telephone interview. Results. We enrolled 389 HZ case patients and 511 matched controls; the median age was 65 and 66 years, respectively. Herpes zoster was associated with family history of HZ (adjusted odds ratio [aOR] = 1.65); association was highest with first-degree or multiple relatives (aOR = 1.87 and 3.08, respectively). Herpes zoster was also associated with prior HZ episodes (aOR = 1.82), sleep disturbance (aOR = 2.52), depression (aOR = 3.81), and recent weight loss (aOR = 1.95). Stress was a risk factor for HZ (aOR = 2.80), whereas a dose-response relationship was not noted. All associations indicated were statistically significant (P < .05). Herpes zoster was not associated with trauma, smoking, tonsillectomy, diet, or reported exposure to pesticides or herbicides (P > .1). Conclusions. We identified several important risk factors for HZ; however, the key attributable causes of HZ remain unknown. PMID:27382600

  3. Management of patients with risk factors

    PubMed Central

    Waldfahrer, Frank

    2013-01-01

    This review addresses concomitant diseases and risk factors in patients treated for diseases of the ears, nose and throat in outpatient and hospital services. Besides heart disease, lung disease, liver disease and kidney disease, this article also covers disorders of coagulation (including therapy with new oral anticoagulants) and electrolyte imbalance. Special attention is paid to the prophylaxis, diagnosis and treatment of perioperative delirium. It is also intended to help optimise the preparation for surgical procedures and pharmacotherapy during the hospital stay. PMID:24403970

  4. Studying Risk Factors Associated with Human Leptospirosis

    PubMed Central

    Kamath, Ramachandra; Swain, Subhashisa; Pattanshetty, Sanjay; Nair, N Sreekumaran

    2014-01-01

    Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression) was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA) to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0), presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02) and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73) and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67) were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still considered as

  5. Risk factors associated with psychiatric readmission.

    PubMed

    Lorine, Kim; Goenjian, Haig; Kim, Soeun; Steinberg, Alan M; Schmidt, Kendall; Goenjian, Armen K

    2015-06-01

    The present study focused on identifying risk factors for early readmission of patients discharged from an urban community hospital. Retrospective chart reviews were conducted on 207 consecutive inpatient psychiatric admissions that included patients who were readmitted within 15 days, within 3 to 6 months, and not admitted for at least 12 months post-discharge. Findings indicated that a diagnosis of schizophrenia/schizoaffective disorder (OR = 18; 95% CI 2.70-117.7; p < 0.05), history of alcohol abuse (OR = 9; 95% CI 1.80-40.60; p < 0.05), number of previous psychiatric hospitalizations (OR = 2; 95% CI 1.28-3.73; p < 0.05), and type of residence at initial admission (e.g., homeless, OR = 29; 95% CI 3.99-217; p < 0.05) were significant risk factors for early readmission, where OR compares readmission group 1 versus group 3 in the multinomial logistic regression. Initial positive urine drug screen, history of drug abuse or incarceration, and legal status at initial admission did not predict early readmission. Reducing the risk factors associated with psychiatric readmissions has the potential to lead to the identification and development of preventative intervention strategies that can significantly improve patient safety, quality of care, well-being, and contain health care expenditures. PMID:25974053

  6. Risk factors associated with facial fractures.

    PubMed

    Batista, Anne Margareth; Ferreira, Fernanda de Oliveira; Marques, Leandro Silva; Ramos-Jorge, Maria Letícia; Ferreira, Meire Coelho

    2012-01-01

    The aim of the present study was to identify risk factors for facial fractures in patients treated in the emergency department of a hospital. The medical charts of 1121 patients treated in an emergency ward over a three-year period were analyzed. The independent variables were gender, age, place of residence (urban or rural area) and type of accident. The dependent variables were fractured mandible, zygoma, maxilla, nasal bone and more than one fractured facial bone. Statistical analysis was performed using the chi-square test (a < 0.05), univariate and multivariate Poisson distributions and the logistic regression analysis (p < 0.20). Maxillofacial trauma was recorded in 790 charts (70.5%), with 393 (35.1%) charts reporting facial fractures. Motorcycle accidents were found to be the main risk factor for mandibular fractures (PR = 1.576, CI = 1.402-1.772) and simultaneous fractures of more than one facial bone (OR = 4.625, CI = 1.888-11.329) as well as the only risk factor for maxillary bone fractures (OR = 11.032, CI = 5.294-22.989). Fractures of the zygomatic and nasal bones were mainly associated with accidents involving animals (PR = 1.206, CI = 1.104-1.317) and sports (OR = 8.710, CI = 4.006-18.936), respectively. The determinant for the majority of facial fractures was motorcycle accidents, followed by accidents involving animals and sports. PMID:22473346

  7. Risk factors for adenocarcinoma of the lung

    SciTech Connect

    Brownson, R.C.; Reif, J.S.; Keefe, T.J.; Ferguson, S.W.; Pritzl, J.A.

    1987-01-01

    The relation between various risk factors and adenocarcinoma of the lung was evaluated in a case-control study. Subjects were selected from the Colorado Central Cancer Registry from 1979-1982 in the Denver metropolitan area. A total of 102 (50 males and 52 females) adenocarcinoma case interviews and 131 (65 males and 66 females) control interviews were completed. The control group consisted of persons with cancers of the colon and bone marrow. The risk estimates associated with cigarette smoking were significantly elevated among males (odds ratio (OR) = 4.49) and females (OR = 3.95) and were found to increase significantly (p less than 0.01) with increasing levels of cigarette smoking for both males and females. For adenocarcinoma in females, the age- and smoking-adjusted odds ratios at different levels of passive smoke exposure followed an increasing overall trend (p = 0.05). After additional adjustment for potential confounders, prior cigarette use remained the most significant predictor of risk of adenocarcinoma among males and females. Analysis restricted to nonsmoking females revealed a risk of adenocarcinoma of 1.68 (95% confidence interval (Cl) = 0.39-2.97) for passive smoke exposure of four or more hours per day. Neither sex showed significantly elevated risk for occupational exposures, although males bordered on significance (OR = 2.23, 95% Cl = 0.97-5.12). The results suggest the need to develop cell type-specific etiologic hypotheses.

  8. Risk factors and cardiovascular disease in Turkey.

    PubMed

    Onat, A

    2001-05-01

    Cardiovascular risk factors as well as morbidity and mortality from coronary heart disease among Turkish adults are herein reviewed. Lipids and lipoproteins are in focus, but other relevant risk factors are also discussed. Turks have distinctively low levels of total and high-density lipoprotein (HDL)-cholesterol, associated with high levels of hepatic lipase and fasting triglycerides. In addition, physical inactivity is common in both genders; close to 60% of men have the smoking habit, while obesity is common among Turkish women leading to a high prevalence of hypertension and diabetes in them. These factors probably account for the unanticipated fact that Turkish adults have the pattern of causes of death similar to a developed population, although the process of industrialization is ongoing, the structure of its population is young and overall cholesterol levels are comparatively low. The age-standardized coronary heart disease death rate is estimated to rank among the highest in Europe. The leading independent predictors of coronary events and death [systolic blood pressure, total/HDL-cholesterol ratio, followed by diabetes and (central) obesity] are related to the metabolic syndrome, estimated to prevail in 3-4% of adults aged 30 or over, and to underlie one-eighth of cases of coronary disease. Since several adverse factors exhibit a rising trend, primary and secondary prevention of cardiovascular disease must assume a much higher priority in various issues in Turkey than it currently does. PMID:11368991

  9. Perinatal risk factors for acute myeloid leukemia.

    PubMed

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2015-12-01

    Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P < 0.001), with peak risk among persons born in winter. Relative to persons born in summer (June-August), incidence rate ratios for AML were 1.72 (95 % CI 1.25-2.38; P = 0.001) for winter (December-February), 1.37 (95 % CI 0.99-1.90; P = 0.06) for spring (March-May), and 1.27 (95 % CI 0.90-1.80; P = 0.17) for fall (September-November). Other risk factors for AML included high fetal growth, high gestational age at birth, and low maternal education level. These findings did not vary by sex or age at diagnosis. Sex, birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML. PMID:26113060

  10. Risk Factors for Hepatocellular Carcinoma in India

    PubMed Central

    Kar, Premashis

    2014-01-01

    Hepatocellular carcinoma (HCC) is an important cause of death all over the world, more so in Asia and Africa. The representative data on epidemiology of HCC in India is very scanty and cancer is not a reportable disease in India and the cancer registries in India are mostly urban. 45 million people who are suffering from chronic Hepatitis B virus (HBV) infection and approximately 15 million people who are afflicted with chronic Hepatitis C virus (HCV) infection in India. HBV and HCV infection is considered an important etiologic factor in HCC. Positive association between HCC and consumption of alcohol where alcohol contribute as a cofactor for hepatotoxins and hepatitis viruses. Aflatoxin contamination in the diets, Hepatitis B virus infection and liver cirrhosis in Andhra Pradesh, India and direct chronic exposure to aflatoxins was shown to cause liver cirrhosis. Cirrhosis of liver of any cause lead to develop about 70%–90% of HCC. Aflatoxin interact synergistically with Hepatitis B virus (HBV)/Hepatitis C virus (HCV) infection which increase the risk of HCC. HBV infection, HBV infection with Aflatoxin exposure, viral infection and alcohol consumption leading to overt cirrhosis of the liver, alcohol consumption leading to cirrhosis of the liver with viral infection are the predominant risk factor for the development of HCC. HCV and alcohol are also associated with HCC in India. Indians develop diabetes at younger age, Asians have strong genetic susceptibility for type II diabetes. Diabetes mellitus is identified as a risk factor for HCC. Prevention of viral infection by universal vaccination against hepatitis virus, HCC surveillance program, preventing alcoholic liver diseases, fungal contamination of grains and ground crops to prevent basically Aflatoxin exposure are important measures to prevent liver diseases and HCC among those at risk. PMID:25755609

  11. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    PubMed

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  12. Identification of Caries Risk Factors in Toddlers

    PubMed Central

    Fontana, M.; Jackson, R.; Eckert, G.; Swigonski, N.; Chin, J.; Zandona, A. Ferreira; Ando, M.; Stookey, G.K.; Downs, S.; Zero, D.T.

    2011-01-01

    The purpose of this study was to identify risk factors to predict caries progression in toddlers in primary-healthcare settings for the cost-effective targeting of preventive and referral strategies. We examined 329 children (26 ± 6 mos old) twice, one year apart, in Indiana, USA. A 107-item structured interview was used to collect information from the primary caregiver and child on factors/beliefs/perceptions/behaviors that could affect caries development, transmission of bacteria, medical-dental health, and access to care. Bacterial levels, gingivitis, dental plaque, and caries experience were assessed. Multiple-variable logistic regression models of caries progression toward cavitation included family caries experience, transmission-related behaviors, dietary factors, health beliefs, and lower income, but differed in selected predictors/predictive power by race/ethnicity. Addition of clinical variables did not significantly improve the prediction. PMID:21173434

  13. Association of Age Related Macular Degeneration and Age Related Hearing Impairment

    PubMed Central

    Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

    2016-01-01

    Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

  14. Risk Factors for Idiopathic Optic Neuritis Recurrence

    PubMed Central

    Zhang, Yu-Jiao; Li, Kaijun; He, Jian-Feng

    2014-01-01

    Background Approximately 30–50% of idiopathic optic neuritis (ION) patients experience one or multiple episodes of recurrence. The aim of this study was to search for risk factors for ION recurrence. Methods Clinical data on hospitalized patients diagnosed with ION between January 2003 and January 2011 at the First Affiliated Hospital of Guangxi Medical University were retrospectively collected. Univariate and multivariate analyses were performed on factors that might cause ION recurrence. In total, 115 ION cases (32 recurrent and 83 non-recurrent cases) with complete data were analyzed. The length of the follow-up period ranged from 12 to 108 months (median: 42 months). Results The univariate analysis showed that the recurrence rate for unilateral ION was higher than that for bilateral ION (40% vs. 12%, p = 0.001). Underlying diseases had a significant impact on recurrence (p<0.001): the recurrence rates due to neuromyelitis optica (NMO), multiple sclerosis (MS), demyelinating lesions alone of the central nervous system, and unknown causes were 89%, 70%, 41%, and 8.7%, respectively. The multivariate analysis showed that the factors causing relatively high recurrence rates included NMO (odds ratio [OR], 73.5; 95% confidence interval [CI], 7.3 to 740.9), MS (OR, 33.9; 95% CI, 5.2 to 222.2), and demyelinating lesions alone (OR, 8.9; 95% CI, 2.3 to 34.4), unilateral involvement (OR, 5.7; 95% CI, 1.5 to 21.3), relatively low initial glucocorticoid dosage (equivalent to ≤100 mg prednisone/day) (OR, 4.3; 95% CI, 1.0 to 17.9). Conclusion Underlying diseases, laterality (unilateral or bilateral), and initial glucocorticoid dosage are important risk factors of ION recurrence. Clinical physicians are advised to treat ION patients with a sufficient dose of glucocorticoid in the initial treatment stage to reduce the recurrence risk. PMID:25255372

  15. Risk factors for asthma: is prevention possible?

    PubMed

    Beasley, Richard; Semprini, Alex; Mitchell, Edwin A

    2015-09-12

    Asthma is one of the most common diseases in the world, resulting in a substantial burden of disease. Although rates of deaths due to asthma worldwide have reduced greatly over the past 25 years, no available therapeutic regimens can cure asthma, and the burden of asthma will continue to be driven by increasing prevalence. The reasons for the increase in asthma prevalence have not been defined, which limits the opportunities to develop targeted primary prevention measures. Although associations are reported between a wide range of risk factors and childhood asthma, substantiation of causality is inherently difficult from observational studies, and few risk factors have been assessed in primary prevention studies. Furthermore, none of the primary prevention intervention strategies that have undergone scrutiny in randomised controlled trials has provided sufficient evidence to lead to widespread implementation in clinical practice. A better understanding of the factors that cause asthma is urgently needed, and this knowledge could be used to develop public health and pharmacological primary prevention measures that are effective in reducing the prevalence of asthma worldwide. To achieve this it will be necessary to think outside the box, not only in terms of risk factors for the causation of asthma, but also the types of novel primary prevention strategies that are developed, and the research methods used to provide the evidence base for their implementation. In the interim, public health efforts should remain focused on measures with the potential to improve lung and general health, such as: reducing tobacco smoking and environmental tobacco smoke exposure; reducing indoor and outdoor air pollution and occupational exposures; reducing childhood obesity and encouraging a diet high in vegetables and fruit; improving feto-maternal health; encouraging breastfeeding; promoting childhood vaccinations; and reducing social inequalities. PMID:26382999

  16. Risk and protection factors in fatal accidents.

    PubMed

    Dupont, Emmanuelle; Martensen, Heike; Papadimitriou, Eleonora; Yannis, George

    2010-03-01

    This paper aims at addressing the interest and appropriateness of performing accident severity analyses that are limited to fatal accident data. Two methodological issues are specifically discussed, namely the accident-size factors (the number of vehicles in the accident and their level of occupancy) and the comparability of the baseline risk. It is argued that - although these two issues are generally at play in accident severity analyses - their effects on, e.g., the estimation of survival probability, are exacerbated if the analysis is limited to fatal accident data. As a solution, it is recommended to control for these effects by (1) including accident-size indicators in the model, (2) focusing on different sub-groups of road-users while specifying the type of opponent in the model, so as to ensure that comparable baseline risks are worked with. These recommendations are applied in order to investigate risk and protection factors of car occupants involved in fatal accidents using data from a recently set up European Fatal Accident Investigation database (Reed and Morris, 2009). The results confirm that the estimated survival probability is affected by accident-size factors and by type of opponent. The car occupants' survival chances are negatively associated with their own age and that of their vehicle. The survival chances are also lower when seatbelt is not used. Front damage, as compared to other damaged car areas, appears to be associated with increased survival probability, but mostly in the case in which the accident opponent was another car. The interest of further investigating accident-size factors and opponent effects in fatal accidents is discussed. PMID:20159090

  17. Erosion—diagnosis and risk factors

    PubMed Central

    Jaeggi, T.

    2008-01-01

    Dental erosion is a multifactorial condition: The interplay of chemical, biological and behavioural factors is crucial and helps explain why some individuals exhibit more erosion than others. The erosive potential of erosive agents like acidic drinks or foodstuffs depends on chemical factors, e.g. pH, titratable acidity, mineral content, clearance on tooth surface and on its calcium-chelation properties. Biological factors such as saliva, acquired pellicle, tooth structure and positioning in relation to soft tissues and tongue are related to the pathogenesis of dental erosion. Furthermore, behavioural factors like eating and drinking habits, regular exercise with dehydration and decrease of salivary flow, excessive oral hygiene and, on the other side, an unhealthy lifestyle, e.g. chronic alcoholism, are predisposing factors for dental erosion. There is some evidence that dental erosion is growing steadily. To prevent further progression, it is important to detect this condition as early as possible. Dentists have to know the clinical appearance and possible signs of progression of erosive lesions and their causes such that adequate preventive and, if necessary, therapeutic measures can be initiated. The clinical examination has to be done systematically, and a comprehensive case history should be undertaken such that all risk factors will be revealed. PMID:18228059

  18. Allergy: A Risk Factor for Suicide?

    PubMed Central

    Postolache, Teodor T.; Komarow, Hirsh; Tonelli, Leonardo H.

    2008-01-01

    Opinion statement The rates of depression, anxiety, and sleep disturbance (suicide risk factors) are greater in patients with allergic rhinitis than in the general population. The rate of allergy is also greater in patients with depression. Preliminary data suggest that patients with a history of allergy may have an increased rate of suicide. Clinicians should actively inquire to diagnose allergy in patients with depression and depression in patients with allergy. Spring peaks of suicide are highly replicated, but their origin is poorly understood. Preliminary epidemiologic data suggest that seasonal spring peaks in aeroallergens are associated with seasonal spring peaks in suicide. Our research in Brown Norway rats demonstrates that sensitization and exposure to aeroallergens induces anxiety-like and aggressive behaviors as well as allergy-related helper T-cell type 2 (Th2) cytokine gene expression in the prefrontal cortex. Thus, it is possible that sensitization and exposure to aeroallergens, which peak in spring, may be conducive to seasonal exacerbation of suicide risk factors such as anxiety, depression, hostility/ aggression, and sleep disturbance. Connecting allergy with suicide and suicide risk factors adds to previous neurologic literature connecting allergy with migraines and seizure disorders. Our recent report of Th2 (allergy-mediating) cytokine expression in the orbito-frontal cortex of suicide victims should lead to future studies to test the hypothesis that mediators of allergic inflammation in the nasal cavities may result in Th2 cytokine expression in the brain, influencing affect and behavioral modulation. Certain medications used to treat allergy can exacerbate suicide risk factors, potentially worsening suicide risk and even triggering suicide. Systemic (but not topical) corticosteroids have been associated with manic and depressive episodes and mixed mood states. Recently, the US Food and Drug Administration started investigating the

  19. A retrospective investigation into risk factors of sarcoptic mange in dogs.

    PubMed

    Feather, Lucy; Gough, Kevin; Flynn, Robin J; Elsheikha, Hany M

    2010-07-01

    This retrospective study of sarcoptic mange in dogs aimed to identify risk factors for this disease and determine their influence on treatment outcome. Data regarding dog demographics, clinical presentation, diagnostic method, treatment, and outcome were analyzed. No statistical association was found between sex and incidence of sarcoptic mange. However, age of dogs was found to be a risk factor which could increase the chances of dogs contracting sarcoptic mange. The results indicate that the disease predominantly affects young dogs, of all breeds and both sexes, implicating age-related immunity. The most common clinical feature reported was pruritus, with the ear margins preferentially affected. Additionally, contact with other animals played an important role in occurrence of the disease indicating the highly transmissible nature of the disease. PMID:20405144

  20. Kidney and eye diseases: common risk factors, etiological mechanisms, and pathways.

    PubMed

    Wong, Chee Wai; Wong, Tien Yin; Cheng, Ching-Yu; Sabanayagam, Charumathi

    2014-06-01

    Chronic kidney disease is an emerging health problem worldwide. The eye shares striking structural, developmental, and genetic pathways with the kidney, suggesting that kidney disease and ocular disease may be closely linked. A growing number of studies have found associations of chronic kidney disease with age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract. In addition, retinal microvascular parameters have been shown to be predictive of chronic kidney disease. Chronic kidney disease shares common vascular risk factors including diabetes, hypertension, smoking, and obesity, and pathogenetic mechanisms including inflammation, oxidative stress, endothelial dysfunction, and microvascular dysfunction, with ocular diseases supporting the 'Common Soil Hypothesis.' In this review, we present major epidemiological evidence for these associations and explore underlying pathogenic mechanisms and common risk factors for kidney and ocular disease. Understanding the link between kidney and ocular disease can lead to the development of new treatment and screening strategies for both diseases. PMID:24336029

  1. Risk factors of γ-hydroxybutyrate overdosing.

    PubMed

    Korf, Dirk J; Nabben, Ton; Benschop, Annemieke; Ribbink, Kim; van Amsterdam, Jan G C

    2014-01-01

    The aim of this study was to identify in recreational drug users the factors which increase the risk of overdosing (OD) with γ-hydroxybutyrate (GHB). A purposive sample of 45 experienced GHB users was interviewed, equally divided into three groups (never OD, occasional OD, and repeat OD). The repeat OD group scored highest on many risk factors regarding GHB use, the occasional OD group scored intermediate, and the never OD group scored lowest. Participants, whether or not they had overdosed on GHB, most often perceived GHB use (e.g. using more GHB than usual, using GHB doses too closely together) as the main reason for GHB OD, and many participants who had overdosed on GHB reported that they had taken more GHB than usual at their most recent occasion of GHB OD. No significant differences in co-use of GHB with other substances were found between the three groups. Our findings indicate that using GHB in the company of groups of friends probably reduces, but does not eliminate, the risk of OD. PMID:24080792

  2. Risk Factors and Comorbidities for Onychomycosis

    PubMed Central

    Tosti, Antonella

    2015-01-01

    A number of comorbidities and risk factors complicate the successful management of onychomycosis. Underlying conditions and patient characteristics, such as tinea pedis, age, and obesity, contribute to risk, whereas comorbidities, such as diabetes and psoriasis, can increase susceptibility to the disease. There are limited data on treatment effectiveness in these patients. Here, the authors review post hoc analyses of efinaconazole topical solution, 10%, in mild-to-moderate onychomycosis and present new data in terms of age and obesity. The only post hoc analysis to report significant differences so far is gender, where female patients do much better; however, the reasons are unclear. The authors report significant differences in terms of efficacy in obese patients who do not respond as well as those with normal body mass index (P=0.05) and in patients who have their co-existing tinea pedis treated compared to those in whom co-existing tinea pedis was not treated (P=0.025). Although there is a trend to reduced efficacy in older patients and those with co-existing diabetes, differences were not significant. More research is needed in onychomycosis patients with these important risk factors and comorbidities to fully evaluate the treatment challengse and possible solutions. PMID:26705439

  3. Age-Related Changes in the Misinformation Effect.

    ERIC Educational Resources Information Center

    Sutherland, Rachel; Hayne, Harlene

    2001-01-01

    Two experiments examined relation between age-related changes in retention and age-related changes in the misinformation effect. Found large age-related retention differences when participants were interviewed immediately and after 1 day, but after 6 weeks, differences were minimal. Exposure to misleading information increased commission errors.…

  4. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    PubMed Central

    Licastro, Federico; Candore, Giuseppina; Lio, Domenico; Porcellini, Elisa; Colonna-Romano, Giuseppina; Franceschi, Claudio; Caruso, Calogero

    2005-01-01

    The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival

  5. Assessing risk factors for periodontitis using regression

    NASA Astrophysics Data System (ADS)

    Lobo Pereira, J. A.; Ferreira, Maria Cristina; Oliveira, Teresa

    2013-10-01

    Multivariate statistical analysis is indispensable to assess the associations and interactions between different factors and the risk of periodontitis. Among others, regression analysis is a statistical technique widely used in healthcare to investigate and model the relationship between variables. In our work we study the impact of socio-demographic, medical and behavioral factors on periodontal health. Using regression, linear and logistic models, we can assess the relevance, as risk factors for periodontitis disease, of the following independent variables (IVs): Age, Gender, Diabetic Status, Education, Smoking status and Plaque Index. The multiple linear regression analysis model was built to evaluate the influence of IVs on mean Attachment Loss (AL). Thus, the regression coefficients along with respective p-values will be obtained as well as the respective p-values from the significance tests. The classification of a case (individual) adopted in the logistic model was the extent of the destruction of periodontal tissues defined by an Attachment Loss greater than or equal to 4 mm in 25% (AL≥4mm/≥25%) of sites surveyed. The association measures include the Odds Ratios together with the correspondent 95% confidence intervals.

  6. Internet Abuse Risk Factors among Spanish Adolescents.

    PubMed

    Carballo, José L; Marín-Vila, María; Espada, José P; Orgilés, Mireia; Piqueras, José A

    2015-01-01

    Empirical evidence has revealed various factors that contribute to the development and maintenance of Internet abuse. The aim of this paper was to analyze, on a sample of Spanish adolescents, the relationship between Internet abuse and: (1) Personal and interpersonal risk factors, including social skills in both virtual and real-life contexts; (2) Drug use. A total of 814 high school students aged between 13 and 17 participated in this study, and were divided into two groups: Internet Abusers (IA = 173) and Non-Internet Abusers (NIA = 641). Questionnaires were used to analyze Internet and drug use/abuse, as well as social skills, in virtual and real contexts. Various interpersonal risk factors (family and group of friends) were also assessed. IA showed a more severe pattern of Internet and drug use, as well as poorer social skills in both contexts. Moreover, their groups of friends appeared more likely to become involved in risky situations related to Internet and drug abuse. Both IA and NIA showed more adaptive social skills in the virtual context than in the real one. There is a need for further research to build on these findings, with a view to designing specific preventive programs that promote responsible Internet use. PMID:26611139

  7. Preventing delirium in dementia: Managing risk factors.

    PubMed

    Ford, Andrew H

    2016-10-01

    Delirium is a common, disabling medical condition that is associated with numerous adverse outcomes. A number of inter-related factors, including pre-existing cognitive impairment, usually contribute to the development of delirium in a particular susceptible individual. Non-pharmacological approaches to prevention typically target multiple risk factors in a systematic manner (multicomponent interventions). There is generally good evidence that multicomponent interventions reduce the incidence of delirium in hospital populations but there are limited data in people with dementia and those living in the community. It is likely that there is a differential effect of specific interventions in those with cognitive impairment (e.g. people with dementia may respond better to simpler, more pragmatic interventions rather than complex procedures) but this cannot be determined from the existing data. Targeted interventions focussed on hydration, medication rationalization and sleep promotion may also be effective in reducing the incidence of delirium, as well as the active involvement of family members in the care of the elderly hospitalized patient. Hospitalization itself is a potential risk factor for delirium and promising data are emerging of the benefits of home-based care as an alternative to hospitalization but this is restricted to specific sub-populations of patients and is reliant on these services being available. PMID:27621236

  8. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

    Hasanjani Roushan, Mohammad Reza; Moulana, Zahra; Afshar, Zeinab Mohseni; Ebrahimpour, Soheil

    2016-01-01

    Background & Propose: Brucellosis is serious disease around the world, especially in underdeveloped countries. Relapse is major problem in therapy of brucellosis. This study aimed to evaluate risk factors of relapse after treatment in patients. Methods: It is a descriptive-analytic study from 1990 to 2014, in Ayatolla Rohani hospital in Babol, Iran. We studied 980 patients with brucellosis. The studied community included patients infected with brucellosis and the required information was gathered based on their hospital files. The base for recognizing Malta fever were clinical symptoms and Para-clinical sign congruent with infection like as, titer SAT>1:320 and 2-ME>1:160. Patients with relapse and patients without relapse were placed separately in two groups. The data were statistically compared with Spss 16, by Chi-square and Cox–regression tests. Results: Based on this study, treatment regimen is a preventive factor (P=0.000). Moreover, Based on some statistical methods, regimens no. 3 and 4 were introduce preventive factors (P=0.001) and (P=0.004). It should also be noted that findings the same statistical model, factors like gender, age, residence, professional contacts, complications and delay in treatment were also analyzed but none of them are considered as preventive factors. Conclusion: Based our finding, we suggest aminoglycosides (gentamicin or streptomycin with doxycycline) are associated with lower rate of relapse in brucellosis.

  9. Treatment of neovascular age-related macular degeneration: Current therapies

    PubMed Central

    Augustin, Albert J; Scholl, Stefan; Kirchhof, Janna

    2009-01-01

    Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition. PMID:19668562

  10. Cholera risk factors, Papua New Guinea, 2010

    PubMed Central

    2012-01-01

    Background Cholera is newly emergent in Papua New Guinea but may soon become endemic. Identifying the risk factors for cholera provides evidence for targeted prevention and control measures. Methods We conducted a hospital-based case–control study to identify cholera risk factors. Using stool culture as the standard, we evaluated a cholera point of care test in the field. Results 176 participants were recruited: 54 cases and 122 controls. Independent risk factors for cholera were: being over 20 years of age (aOR 2.5; 95%CI 1.1, 5.4), defecating in the open air (or river) (aOR 4.5; 95% CI 1.4, 14.4) and knowing someone who travelled to a cholera affected area (aOR 4.1; 95%CI 1.6, 10.7); while the availability of soap for handwashing at home was protective (aOR 0.41; 95%CI 0.19, 0.87). Those reporting access to a piped water distribution system in the home were twice as likely to report the availability of soap for handwashing. The sensitivity and specificity of the rapid test were 72% (95% CI 47–90) and 71% (95%CI 44–90%). Conclusions Improving population access to the piped water distribution system and sanitation will likely reduce transmission by enabling enhanced hygiene and limiting the contamination of water sources. The One step V. cholerae O1/O139 Antigen Test is of limited utility for clinical decision making in a hospital setting with access to traditional laboratory methods. Settlement dwellers and mobile populations of all age groups should be targeted for interventions in Papua New Guinea. PMID:23126504

  11. Risk factors affecting dental implant survival.

    PubMed

    Vehemente, Valerie A; Chuang, Sung-Kiang; Daher, Shadi; Muftu, Ali; Dodson, Thomas B

    2002-01-01

    Given the predictability of dental implant success, the attention of the scientific community is moving from descriptions of implant success toward a more detailed analysis of factors associated with implant failure. The purposes of this study were (1) to estimate the 1- and 5-year survival of Bicon dental implants and (2) to identify risk factors associated with implant failure in an objective, statistically valid manner. To address the research purposes, we used a retrospective cohort study design and a study sample composed of patients who had one or more implants placed. The predictor variables were grouped into the following categories: demographic, health status, anatomic, implant fixture-specific, prosthetic, perioperative, and ancillary variables. The major outcome variable of interest was implant failure defined as implant removal. Overall implant survival was estimated using the Kaplan-Meier analysis. Risk factors for implant failure were identified using the Cox proportional hazard regression models. The study sample was composed of 677 patients who had 677 implants randomly selected for analysis. The overall 1- and 5-year survival of the Bicon implant system was 95.2% and 90.2%, respectively. After adjusting for other covariates in a multivariate model, both tobacco use (P = .0004) and single-stage implant placement (P = .01) were statistically associated with an increased risk for failure. The results of these analyses suggest that the overall survival of the Bicon dental implant is comparable with other current implant systems. In addition, after controlling for covariates, we identified 2 exposures associated with implant survival, tobacco use and implant staging. Of interest, both of these exposures are under the clinician's control. PMID:12498449

  12. Cardiometabolic risk factors and atrial fibrillation.

    PubMed

    Menezes, Arthur R; Lavie, Carl J; Dinicolantonio, James J; O'Keefe, James; Morin, Daniel P; Khatib, Sammy; Abi-Samra, Freddy M; Messerli, Franz H; Milani, Richard V

    2013-01-01

    Atrial fibrillation (AF) is the most common arrhythmia worldwide; it is a significant risk factor for stroke and embolization, and has an impact on cardiac function. Despite its impact on morbidity and mortality, our understanding of the etiology and pathophysiology of this disease process is still incomplete. Over the past several decades, there has been evidence to suggest that AF has a significant correlation with metabolic syndrome (MetS). Furthermore, AF appears to be more closely related to specific components of MetS compared with others. This article provides an overview of the various components of MetS and their impact on AF. PMID:24448257

  13. Childhood incontinence: risk factors and impact.

    PubMed

    Joinson, Carol

    Continence problems in children can persist into later childhood and have a serious effect on quality of life. Research into its causes and impact is scarce, and useful resources are limited. A Medical Research Council grant is funding a project at the University of Bristol, which aims to improve understanding of the risk factors and outcomes of continence problems in children and adolescents. This article outlines the initial findings, which could help in the production of resources for parents, children and young people. PMID:27386707

  14. Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment

    PubMed Central

    Janevska, Dafina; Chaloska-Ivanova, Viktorija; Janevski, Vlado

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue. This article provides an overview of this disease based on an extensive review of relevant literature. The article summarizes the current risk factors, diagnosis, staging and the management of HCC. PMID:27275318

  15. [Patient's Risk Factors for Perioperative Aspiration Pneumonia].

    PubMed

    Ishikawa, Teruhiko; Isono, Shiroh

    2016-01-01

    This article reviews patient's own risk factors for perioperative aspiration pneumonia. Maintaining the function of the lower esophageal sphincter (LES), the airway protective reflex, and the oral hygiene are the most important to prevent the pneumonia. The LES is adversely affected by excessive stomach distention, some medication given in perioperative periods, and habitual smoking, as well as pathological status such as esophageal hiatus hernia and achalasia. Postapoplectic patients may have insufficient airway protective reflex including swallowing and laryngeal reflex. It is emphasized that the perioperative oral care is increasing in its importance for the prevention of aspiration pneumonia. PMID:27004381

  16. DIETARY CARBOHYDRATE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION, A PROSPECTIVE STUDY FROM THE AGE-RELATED EYE DISEASE STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Cross-sectional studies indicate that diets that provide a higher dietary glycemic index (dGI) are associated with increased risk of age-related macular degeneration (AMD). No prospective studies have addressed this issue. Methods dGI was calculated as the weighted average of GIs from foo...

  17. Nutrient Supplementation for Age-related Macular Degeneration, Cataract, and Dry Eye

    PubMed Central

    Hobbs, Ronald P.; Bernstein, Paul S.

    2014-01-01

    There have been enormous advances in the past decade for the treatment of age-related macular degeneration (AMD); however, these treatments are expensive and require frequent follow-up and injections which place a tremendous burden on both the healthcare system and patients. Consequently, there remains considerable interest in preventing or slowing the progression of AMD requiring treatment. Epidemiological studies have shown that diet is a modifiable AMD risk factor, and nutrient modification is a particularly appealing treatment for AMD due to the perceived universal benefit and relatively low expense. Recently, the age-related eye disease study part two (AREDS2) was concluded and demonstrated further benefit with the addition of lutein and zeaxanthin as a replacement for the β-carotene of the previous generation formulation. The addition of omega-3 essential fatty acids did not show an added benefit. This review aims to highlight some of the evidenced based body of knowledge that has been accumulated from recent studies regarding the use of nutritional supplements and their effect on AMD, cataracts, and dry eyes. PMID:25709776

  18. Update on the role of genetics in the onset of age-related macular degeneration

    PubMed Central

    Francis, Peter James; Klein, Michael L

    2011-01-01

    Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century. PMID:21887094

  19. "New Old Pathologies": AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS).

    PubMed

    Nelson, Peter T; Trojanowski, John Q; Abner, Erin L; Al-Janabi, Omar M; Jicha, Gregory A; Schmitt, Frederick A; Smith, Charles D; Fardo, David W; Wang, Wang-Xia; Kryscio, Richard J; Neltner, Janna H; Kukull, Walter A; Cykowski, Matthew D; Van Eldik, Linda J; Ighodaro, Eseosa T

    2016-06-01

    The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists. Analyses of large autopsy series, biomarker studies, and genomics analyses have provided important insights about AD and shed light on previously unrecognized conditions, enabling a deeper understanding of neurodegenerative diseases in general. After demonstrating the importance of correct disease classification for AD and primary age-related tauopathy, we emphasize the public health impact of an underappreciated AD "mimic," which has been termed "hippocampal sclerosis of aging" or "hippocampal sclerosis dementia." This pathology affects >20% of individuals older than 85 years and is strongly associated with cognitive impairment. In this review, we provide an overview of current hypotheses about how genetic risk factors (GRN, TMEM106B, ABCC9, and KCNMB2), and other pathogenetic influences contribute to TDP-43 pathology and hippocampal sclerosis. Because hippocampal sclerosis of aging affects the "oldest-old" with arteriolosclerosis and TDP-43 pathologies that extend well beyond the hippocampus, more appropriate terminology for this disease is required. We recommend "cerebral age-related TDP-43 and sclerosis" (CARTS). A detailed case report is presented, which includes neuroimaging and longitudinal neurocognitive data. Finally, we suggest a neuropathology-based diagnostic rubric for CARTS. PMID:27209644

  20. Comparative Safety and Tolerability of Anti-VEGF therapy in Age-Related Macular Degeneration

    PubMed Central

    Modi, Yasha S.; Tanchon, Carley; Ehlers, Justis P

    2015-01-01

    Neovascular age-related macular degeneration (NVAMD) is one of the leading causes of blindness. Over the last decade, the treatment of NVAMD has been revolutionized by the development intravitreal anti-vascular endothelial growth factor (VEGF) therapies. Several anti-VEGF medications are used for the treatment of NVAMD. The safety and tolerability of these medications deserve review given the high prevalence of NVAMD and the significant utilization of these medications. Numerous large randomized clinical trials have not shown any definitive differential safety relative to ocular or systemic safety of these medications. Intravitreal anti-VEGF therapy does appear to impact systemic VEGF levels, but the implications of these changes remain unclear. One unique safety concern relates drug compounding and the potential risks of contamination, specifically for bevacizumab. Continued surveillance for systemic safety concerns, particularly for rare events is merited. Overall these medications are well tolerated and effective in the treatment of NVAMD. PMID:25700714

  1. Identification of a Rare Coding Variant in Complement 3 Associated with Age-related Macular Degeneration

    PubMed Central

    Zhan, Xiaowei; Larson, David E.; Wang, Chaolong; Koboldt, Daniel C.; Sergeev, Yuri V.; Fulton, Robert S.; Fulton, Lucinda L.; Fronick, Catrina C.; Branham, Kari E.; Bragg-Gresham, Jennifer; Jun, Goo; Hu, Youna; Kang, Hyun Min; Liu, Dajiang; Othman, Mohammad; Brooks, Matthew; Ratnapriya, Rinki; Boleda, Alexis; Grassmann, Felix; von Strachwitz, Claudia; Olson, Lana M.; Buitendijk, Gabriëlle H.S.; Hofman, Albert; van Duijn, Cornelia M.; Cipriani, Valentina; Moore, Anthony T.; Shahid, Humma; Jiang, Yingda; Conley, Yvette P.; Morgan, Denise J.; Kim, Ivana K.; Johnson, Matthew P.; Cantsilieris, Stuart; Richardson, Andrea J.; Guymer, Robyn H.; Luo, Hongrong; Ouyang, Hong; Licht, Christoph; Pluthero, Fred G.; Zhang, Mindy M.; Zhang, Kang; Baird, Paul N.; Blangero, John; Klein, Michael L.; Farrer, Lindsay A.; DeAngelis, Margaret M.; Weeks, Daniel E.; Gorin, Michael B.; Yates, John R.W.; Klaver, Caroline C.W.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Weber, Bernhard H.F.; Wilson, Richard K.; Heckenlively, John R.; Chew, Emily Y.; Stambolian, Dwight; Mardis, Elaine R.; Swaroop, Anand; Abecasis, Goncalo R.

    2013-01-01

    Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry matched controls revealed two large-effect rare variants; previously described R1210C in the CFH gene (fcase = 0.51%, fcontrol = 0.02%, OR = 23.11), and newly identified K155Q in the C3 gene (fcase = 1.06%, fcontrol = 0.39%, OR = 2.68). The variants suggest decreased inhibition of C3 by Factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology. PMID:24036949

  2. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    MedlinePlus

    ... lymphocytic leukemia? What are the risk factors for acute lymphocytic leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  3. What Are the Risk Factors for Bone Cancer?

    MedlinePlus

    ... bone cancer? What are the risk factors for bone cancer? A risk factor is anything that affects your ... are caused by defects (mutations) in certain genes. Osteosarcomas Children with certain rare inherited syndromes have an ...

  4. Epidemiology of Down syndrome: new insight into the multidimensional interactions among genetic and environmental risk factors in the oocyte.

    PubMed

    Ghosh, Sujoy; Hong, Chang-Sook; Feingold, Eleanor; Ghosh, Papiya; Ghosh, Priyanka; Bhaumik, Pranami; Dey, Subrata Kumar

    2011-11-01

    Down syndrome birth is attributable to multiple maternal risk factors that include both genetic and environmental challenges, but there is limited understanding of the complicated interactions among these factors. In the present study, a case-control analysis of approximately 400 infants with or without suspected Down syndrome reported between 2003 and 2009 and their parents in and around Kolkata, India, was conducted. Maternal exposure to 2 environmental risk factors (smokeless chewing tobacco and oral contraceptive pills) was recorded, and families were genotyped with microsatellite markers to establish the origin of nondisjunction errors as well as recombination patterns of nondisjoined chromosome 21. With logistic regression models, the possible interactions among all of these risk factors, as well as with maternal age, were explored. Smokeless chewing tobacco was associated with significant risk for meiosis II nondisjunction and achiasmate (nonexchange) meiosis I error among young mothers. By contrast, the risk due to oral contraceptive pills was associated with older mothers. Study results suggest that the chewing tobacco risk factor operates independently of the maternal age effect, whereas contraceptive pill-related risk may interact with or exacerbate age-related risk. Moreover, both risk factors, when present together, exhibited a strong age-dependent effect. PMID:21957181

  5. Epigenetic Risk Factors in PTSD and Depression

    PubMed Central

    Raabe, Florian Joachim; Spengler, Dietmar

    2013-01-01

    Epidemiological and clinical studies have shown that children exposed to adverse experiences are at increased risk for the development of depression, anxiety disorders, and posttraumatic stress disorder (PTSD). A history of child abuse and maltreatment increases the likelihood of being subsequently exposed to traumatic events or of developing PTSD as an adult. The brain is highly plastic during early life and encodes acquired information into lasting memories that normally subserve adaptation. Translational studies in rodents showed that enduring sensitization of neuronal and neuroendocrine circuits in response to early life adversity are likely risk factors of life time vulnerability to stress. Hereby, the hypothalamic-pituitary-adrenal (HPA) axis integrates cognitive, behavioral, and emotional responses to early-life stress and can be epigenetically programed during sensitive windows of development. Epigenetic mechanisms, comprising reciprocal regulation of chromatin structure and DNA methylation, are important to establish and maintain sustained, yet potentially reversible, changes in gene transcription. The relevance of these findings for the development of PTSD requires further studies in humans where experience-dependent epigenetic programing can additionally depend on genetic variation in the underlying substrates which may protect from or advance disease development. Overall, identification of early-life stress-associated epigenetic risk markers informing on previous stress history can help to advance early diagnosis, personalized prevention, and timely therapeutic interventions, thus reducing long-term social and health costs. PMID:23966957

  6. Stroke Prevention: Managing Modifiable Risk Factors

    PubMed Central

    Di Legge, Silvia; Koch, Giacomo; Diomedi, Marina; Stanzione, Paolo; Sallustio, Fabrizio

    2012-01-01

    Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors) clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke. PMID:23213626

  7. Occupational risk factors for Wilms' tumor

    SciTech Connect

    Bunin, G.; Kramer, S.; Nass, C.; Meadows, A.

    1986-09-01

    A matched case-control study of Wilms' tumor investigated parental occupational risk factors. Cases diagnosed in 1970-1983 were identified through a population-based tumor registry and hospital registries in the Greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date (+/- 3 years), and the area code and exchange of the case's telephone number at diagnosis. Parents of 100 matched pairs were interviewed by telephone. Parents of patients and controls were generally similar in demographic characteristics, except that mothers differed in religion. Published schemes were used to group jobs into clusters of similar exposures and to determine exposures from industry and job title. Analyses were done for preconception, pregnancy, and postnatal time periods. More case than control fathers had jobs in a cluster that includes machinists and welders (odds ratios (ORs) = 4.0-5.7, p less than or equal to 0.04). Paternal exposures to lead, silver, tin, and iron (some exposures of this cluster) were associated with Wilms' tumor in some analyses, with moderate odds ratios (ORs = 1.5-3.4). In general, the highest odds ratios were found for the preconception period among the genetic (prezygotic) cases. No maternal job clusters or exposures gave significantly elevated odds ratios. These results support a previous finding that lead is a risk factor, but not radiation, hydrocarbon, or boron exposures.

  8. Smoking: A risk factor for vascular disease.

    PubMed

    Gordon, Phyllis; Flanagan, Patty

    2016-09-01

    Smoking in the United States includes at least 16% of the adults, 24% of high school students, nearly 8% of middle school students and is more prevalent in men than women; however, a decline in smoking has been documented in recent years. Cardiovascular disease continues to be a leading cause of death. Smoking is identified as a significant risk factor for cardiovascular disease, carotid disease, and peripheral artery disease with peripheral artery disease documented in 5%-10% of all Americans. Smoking is also a significant risk factor in the development of abdominal aortic aneurysm in 7% of men aged 65-75 years with a smoking history. Toxic chemicals found in tobacco smoke are reported at 7,357 chemical compounds including the addictive chemical of nicotine. A substantial number of large studies and well-known trials have identified an increase in proinflammatory cells and cellular processes in the smoker diagnosed with atherosclerosis and in the mechanism attributed to abdominal aortic aneurysm development. The cost of smoking to health care is significant, and smoking cessation can demonstrate benefits to health improvement and the cost of health care. PMID:27568314

  9. Genetic risk factors in Alzheimer's disease.

    PubMed Central

    Tilley, L; Morgan, K; Kalsheker, N

    1998-01-01

    Following a brief introduction and discussion of the pathological features of Alzheimer's disease, the main emphasis of this review article will be the genetic factors that have been implicated in this disease. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial Alzheimer's disease will be discussed. These are well characterised but account for only a small proportion of Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease. Many of these are controversial and studies have shown conflicting results, which are discussed in this section. Finally, a brief discussion of some of the mechanisms suggested to play a role in the pathogenesis of Alzheimer's disease is included. It is hoped that this will show why particular genes have been implicated in Alzheimer's disease and how they might be able to influence the development of the disease. PMID:10193509

  10. [Perception of health risks: psychological and social factors].

    PubMed

    Kurzenhäuser, S; Epp, A

    2009-12-01

    This article reviews central findings and current developments of psychological and sociological research on the perception of health risks. Risk perception is influenced by numerous psychological, social, political, and cultural factors. These factors can be categorized into (a) risk characteristics, (b) characteristics of the risk perceiving person and his/her situation, and (c) characteristics of risk communication. Thus, besides individual cognitive and affective processing of risk information, social processes of risk amplification (e.g., media effects) are also involved in the construction of individual risk perceptions. We discuss the recommendations for health risk communication that follow from these findings with regard to different communication goals. PMID:19862487

  11. What Are the Risk Factors for Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... is a risk factor for skin cancer, while smoking is a risk factor for cancer of the lung and several ... affected. Factors with uncertain or unproven effects Smoking Smoking may increase the risk of getting a carcinoid tumor of the small ...

  12. What Are the Risk Factors for Thymus Cancer?

    MedlinePlus

    ... cancer? What are the risk factors for thymus cancer? A risk factor is anything that affects your chance of getting ... Back to top » Guide Topics What Is Thymus Cancer? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating ...

  13. Risk Factors for Drug Use in Rural Adolescents.

    ERIC Educational Resources Information Center

    Farrell, Albert D.; And Others

    1992-01-01

    Tested relevance of risk-factor model for predicting drug use among rural seventh graders (n=235). Nineteen of 20 risk factors were significantly related to at least 1 category of drug use. Subset of 10 risk factors was significantly associated with prevalence and frequency of use of cigarettes, beer and wine, hard liquor, marijuana, and other…

  14. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level. PMID:26401926

  15. The Association Between Subretinal Drusenoid Deposits in Older Adults in Normal Macular Health and Incident Age-Related Macular Degeneration

    PubMed Central

    Huisingh, Carrie; McGwin, Gerald; Neely, David; Zarubina, Anna; Clark, Mark; Zhang, Yuhua; Curcio, Christine A.; Owsley, Cynthia

    2016-01-01

    Purpose Subretinal drusenoid deposits (SDD) have been associated with the progression to late age-related macular degeneration (AMD). To determine whether SDD in eyes in normal macular health increases risk for early AMD, this study examined the association between presence of SDD at baseline in a cohort of older adults in normal macular health and incident AMD 3 years later. Methods Subjects enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) were assessed for the presence of SDD using color fundus photos, infrared reflectance and fundus autofluorescence images, and spectral-domain optical coherence tomography volumes. The study sample included 799 eyes from 455 participants in normal macular health per grading of color fundus photographs using the 9-step Age-Related Eye Disease Study (AREDS) classification system. Age-related macular degeneration was defined as eyes having an AREDS grade ≥2 at the 3-year follow-up. Results Twenty-five percent of participants had SDD in one or both eyes at baseline. At follow-up visit, 11.9% of eyes in the sample developed AMD. Compared to eyes without SDD, those with SDD were 2.24 (95% confidence interval [CI] 1.36–3.70) times more likely to have AMD at follow-up. After adjusting for age, C-reactive protein quartile, and family history of AMD, the association persisted. Conclusions Results suggest that SDD in older eyes with normal macular health as defined by the AREDS scale is a risk factor for the development of early AMD. Older adults in seemingly normal macular health yet having SDD may warrant closer clinical monitoring for the possible onset of early AMD. PMID:26906160

  16. Optical Coherence Tomography Updates on Clinical and Technical Developments. Age-Related Macular Degeneration: Drusen and Geographic Atrophy

    NASA Astrophysics Data System (ADS)

    Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Holz, Frank G.

    Age-related macular degeneration (AMD) is a complex disease with both genetic and environmental factors influencing its development. With the advent of high-resolution OCT imaging, the characterization of drusen in AMD has become possible. The in vivo morphologic characteristics imaged with SD-OCT may represent distinct subclasses of drusen variants, may relate closely to ultrastructural drusen elements identified in donor eyes, and may be useful imaging biomarkers for disease severity or risk of progression [Khanifar et al. Ophthalmology 115(11):1883-1890, 2008].

  17. Radiation Therapy for Neovascular Age-related Macular Degeneration

    SciTech Connect

    Kishan, Amar U.; Modjtahedi, Bobeck S.; Morse, Lawrence S.; Lee, Percy

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  18. Retinal phagocytes in age-related macular degeneration

    PubMed Central

    Kim, Soo-Young

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in industrial countries. Vision loss caused by AMD results from geographic atrophy (dry AMD) and/or choroidal neovascularization (wet AMD). Presently, the etiology and pathogenesis of AMD is not fully understood and there is no effective treatment. Oxidative stress in retinal pigment epithelial (RPE) cells is considered to be one of the major factors contributing to the pathogenesis of AMD. Also retinal glia, as scavengers, are deeply related with diseases and could play a role. Therefore, therapeutic approaches for microglia and Müller glia, as well as RPE, may lead to new strategies for AMD treatment. This review summarizes the pathological findings observed in RPE cells, microglia and Müller glia of AMD murine models. PMID:26052551

  19. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2015-07-01

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD. PMID:25524721

  20. Environmental risk factors of systemic sclerosis.

    PubMed

    Marie, Isabelle; Gehanno, Jean-François

    2015-09-01

    Systemic sclerosis (SSc) has a complex pathogenesis. Although, there is a growing evidence that environmental factors have an impact on alterations and modulation of epigenetic determinants, resulting in SSc onset and progression. A marked correlation has thus been found between SSc onset and occupational exposure to crystalline silica and the following organic solvents: white spirit, aromatic solvents, chlorinated solvents, trichloroethylene, and ketones; the risk associated with high cumulative exposure to silica and organic solvents further appears to be strongly increased in SSc. Altogether, occupational exposure should be systematically checked in all SSc patients at diagnosis, as (1) exposed patients seem to develop more severe forms of SSc and (2) the identification of the occupational agents will allow its interruption, which may lead to potential improvement of SSc outcome. By contrast, based on current published data, there is insufficient evidence that exposure to other chemical agents (including notably pesticides as well as personal care such as silicone and hair dye), physical agents (ionizing radiation, ultraviolet radiation, electric and magnetic fields), and biological agents (infections and diet, foods, and dietary contaminants) is a causative factor of SSc. Further investigations are still warranted to identify other environmental factors that may be associated with SSc onset and progression. PMID:26141606

  1. Risk factors of uveitis in ankylosing spondylitis

    PubMed Central

    Sun, Li; Wu, Rui; Xue, Qin; Wang, Feng; Lu, Peirong

    2016-01-01

    Abstract Background: Uveitis is the most common extra-articular manifestation in patients with ankylosing spondylitis (AS). The prevalence and characteristics of uveitis in AS have been studied in previous literatures, whereas its associated risk factors have not been clarified. Therefore, this study analyzed the risk factors of uveitis in patients with AS. Methods: A total of 390 patients with AS who fulfilled the modified New York criteria were enrolled from January to December in 2015. The history of uveitis was accepted only if diagnosed by ophthalmologists. The medical records of the patients were retrospectively reviewed and associated information was collected, such as disease duration, HLA-B27, and the number of peripheral arthritis. Hip-joint lesion was identified by imaging examination. Meanwhile, biochemical examinations were performed to determine the patient's physical function. Results: Of 390 patients with AS (80.5% male, mean age 33.3 years), 38 (9.7%) had experienced 1 or more episodes of uveitis. The incidence rate for hip-joint lesion was obviously higher for patients with uveitis than the nonuveitis group (44.7% vs 22.2%; P < 0.01). The number of peripheral arthritis was also larger for the uveitis group than nonuveitis group (2.18 ± 0.23 vs 0.55 ± 0.04; P < 0.001). Meanwhile, patients with uveitis had a significantly higher level of antistreptolysin O (ASO) and circulating immune complex (CIC) than those without (P < 0.05 and P < 0.0001, respectively). However, there were no significant differences in disease duration, HLA-B27, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) between the 2 groups. Binary logistic regression results showed that ASO (OR = 12.2, 95% CI:3.6–41.3, P < 0.01) and the number of peripheral arthritis (OR = 4.1, 95%CI:2.6–6.3, P < 0.01) are significantly associated with uveitis in AS. Conclustion: This study provides some evidence that hip-joint lesion, the number of

  2. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

  3. Inflammation and its role in age-related macular degeneration.

    PubMed

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms. PMID:26852158

  4. Risk Factors of Sudden Infant Death Syndrome and Risk Factors for Sleep Disturbances

    ERIC Educational Resources Information Center

    Kelmanson, Igor A.

    2011-01-01

    Relationship between major risk factors of sudden infant death syndrome (SIDS) and sleep disorders in the infants is the subject of review and discussion. Improper micro-environmental characteristics (especially poor environmental organisation and lack of developmental stimulation), pre-term delivery and/or infant low birth weight, prone sleep…

  5. [Age-related factors of psychopathology of impulse control disorders].

    PubMed

    Shiurkute, A

    1999-01-01

    15 children and adolescents with impulse control disorders (mean age 12.9 years) were examined. These disorders were presented as dromomania, kleptomania, aggressive-sadistic actions, tricholillomania, pyromania; a combination of different types was observed in some cases. Schizophrenia was diagnosed in 7 cases, affective disorders--in 8 patients. Independently of the nosologic unity of the disease, development of the impulse control disorders took place in affective disorders which manifested either by monopolar course (depression) (11 cases), or by bypolar attacks with unclear outlines of the phases (4 patients). Psychopathology of impulse control disorders in children and juveniles was analogous to that of the adults, however, their structure wasn't so complex and development of the phases wasn't so clear. PMID:11530454

  6. Competing hazards with shared unmeasured risk factors.

    PubMed

    Hill, D H; Axinn, W G; Thornton, A

    1993-01-01

    "The present paper develops a generalization of the standard discrete-time competing hazards model that allows for the types of stochastic dependencies resulting from shared unmeasured risk factors. An empirical example is provided using the process by which young women form their first conjugal residential union, with married and unmarried cohabitation representing the competing alternatives. The results suggest considerable and significant similarity of the alternatives in terms of the unmeasurables. It is also shown that, as a result, the independence assumption leads to substantially biased estimates of the net marriage and net cohabitation survival functions." The data concern a cohort of white children born in Detroit, Michigan, in 1961 and their mothers, followed up to 1985. PMID:12318164

  7. Birth defects: Risk factors and consequences

    PubMed Central

    Oliveira, Camila Ive Ferreira; Fett-Conte, Agnes Cristina

    2013-01-01

    Birth defects (BDs) or congenital anomalies include all structural and functional alterations in embryonic or fetal development resulting from genetic, environmental or unknown causes, which result in physical and/or mental impairment. BDs occur in about 3% of newborn babies and in most cases of pregnancy loss. BDs are a very complex and heterogeneous group of single or multiple changes that, in most cases, are of unknown etiology. Among the risk factors are advanced maternal and paternal ages, parental consanguinity, teratogenic agents such as infectious agents and drugs, and poor nutrition, in particular folic acid deficiency. One of the consequences of these defects is the high death rate within the first year of life. Information on BDs is becoming increasingly more important throughout the world so that preventive measures can be taken. Knowledge of BDs enables the development of therapeutic and preventive strategies besides adequate genetic counseling.

  8. Calciphylaxis: Risk Factors, Diagnosis, and Treatment

    PubMed Central

    Nigwekar, Sagar U.; Kroshinksy, Daniela; Nazarian, Rosalynn M.; Goverman, Jeremy; Malhotra, Rajeev; Jackson, Vicki Ann; Kamdar, Mihir M.; Steele J.R., David; Thadhani, Ravi I.

    2015-01-01

    Calciphylaxis is a rare but devastating condition that has continued to challenge the medical community since its early descriptions in the scientific literature many decades ago. It is predominantly seen in chronic kidney failure patients treated with dialysis (uremic calciphylaxis) but is also described in patients with earlier stages of chronic kidney disease and with normal renal function. In this In Practice feature, we review the available medical literature regarding risk factors, diagnosis, and treatment of both uremic and non-uremic calciphylaxis. High quality evidence for the evaluation and management of calciphylaxis is lacking at this time due to its rare incidence, poorly understood pathogenesis, and the relative paucity of collaborative research efforts. We hereby provide a summary of recommendations developed by the Massachusetts General Hospital's Multi-disciplinary Calciphylaxis Team for calciphylaxis patients. PMID:25960299

  9. Depression in athletes: prevalence and risk factors.

    PubMed

    Wolanin, Andrew; Gross, Michael; Hong, Eugene

    2015-01-01

    Depression affects an estimated 6.7% of today's adult population in a 12-month period. The prevalence rates for certain age groups, such as young adults and older adults, are higher. There are approximately 400,000 National Collegiate Athletic Association student athletes competing each year and 5 to 7 million high school student athletes involved in competitive interscholastic sports. Given such a high prevalence rate in certain age groups and a large denominator pool of athletes, past notions that athletes are devoid of mental health issues have come under scrutiny by sports medicine providers. Initial data suggest that athletes are far from immune to depression. The purpose of this article was to review the current research on athletes and depression; particularly this article will provide an overview of studies, which have investigated the rate of depression among athletes, and discuss relevant risk factors, which may contribute to depression among athletes. PMID:25574886

  10. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood. PMID:24434909

  11. Hepatocellular carcinoma: epidemiology and risk factors

    PubMed Central

    Kew, Michael C

    2014-01-01

    Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron accumulation in hereditary hemochromatosis and dietary iron overload in the Black African population and membranous obstruction of the inferior cava

  12. Nitroxide pharmaceutical development for age-related degeneration and disease

    PubMed Central

    Zarling, Jacob A.; Brunt, Vienna E.; Vallerga, Anne K.; Li, Weixing; Tao, Albert; Zarling, David A.; Minson, Christopher T.

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  13. Differences in Risk Factors for Recurrent Versus Incident Preterm Delivery

    PubMed Central

    Grantz, Katherine L.; Hinkle, Stefanie N.; Mendola, Pauline; Sjaarda, Lindsey A.; Leishear, Kira; Albert, Paul S.

    2015-01-01

    Risk factors for preterm delivery have been described, but whether risk factors differ in the context of prior preterm delivery history is less understood. We assessed whether known risk factors were different in women with versus without prior preterm delivery using medical records of the first and second singleton deliveries in 25,820 Utah women (2002–2010). Longitudinal transition models with modified Poisson regression calculated adjusted relative risks and 95% confidence intervals, with multiplicative interactions between each preterm risk factor and prior preterm delivery status to explore whether risk factors varied between incident and recurrent preterm delivery at <37 weeks. Fewer second pregnancy factors were associated with recurrent preterm delivery, including alcohol, thyroid disease, and depression. Smoking was associated with increased risk for incident (relative risk (RR) = 1.95, 95% confidence interval (CI): 1.53, 2.49) but not recurrent (RR = 1.09, 95% CI: 0.71, 1.19) preterm delivery, whereas alcohol was associated with an increased risk for recurrent (RR = 2.38, 95% CI: 1.53, 3.71) but not incident (RR = 0.98, 95% CI: 0.67, 1.43; Pinteraction = 0.02 and <0.01) preterm delivery, respectively. Prior term delivery did not necessarily confer protection from known second pregnancy preterm delivery risk factors. In the setting of a prior preterm delivery, many risk factors did not persist. Prior preterm delivery history is important when assessing subsequent preterm delivery risk factors. PMID:26033931

  14. Differences in risk factors for recurrent versus incident preterm delivery.

    PubMed

    Grantz, Katherine L; Hinkle, Stefanie N; Mendola, Pauline; Sjaarda, Lindsey A; Leishear, Kira; Albert, Paul S

    2015-07-15

    Risk factors for preterm delivery have been described, but whether risk factors differ in the context of prior preterm delivery history is less understood. We assessed whether known risk factors were different in women with versus without prior preterm delivery using medical records of the first and second singleton deliveries in 25,820 Utah women (2002-2010). Longitudinal transition models with modified Poisson regression calculated adjusted relative risks and 95% confidence intervals, with multiplicative interactions between each preterm risk factor and prior preterm delivery status to explore whether risk factors varied between incident and recurrent preterm delivery at <37 weeks. Fewer second pregnancy factors were associated with recurrent preterm delivery, including alcohol, thyroid disease, and depression. Smoking was associated with increased risk for incident (relative risk (RR) = 1.95, 95% confidence interval (CI): 1.53, 2.49) but not recurrent (RR = 1.09, 95% CI: 0.71, 1.19) preterm delivery, whereas alcohol was associated with an increased risk for recurrent (RR = 2.38, 95% CI: 1.53, 3.71) but not incident (RR = 0.98, 95% CI: 0.67, 1.43; Pinteraction = 0.02 and <0.01) preterm delivery, respectively. Prior term delivery did not necessarily confer protection from known second pregnancy preterm delivery risk factors. In the setting of a prior preterm delivery, many risk factors did not persist. Prior preterm delivery history is important when assessing subsequent preterm delivery risk factors. PMID:26033931

  15. [Epidemiology and risk factors of testicular tumours].

    PubMed

    Kozłowski, Piotr; Starosławska, Elżbieta; Szumiło, Justyna; Jankiewicz, Małgorzata; Kozłowska, Magdalena; Burdan, Franciszek

    2016-04-01

    Testicular tumours are rare neoplasms, which most commonly affects men aged 25 to 35 years. Among young adult males it is the most common cause of testicular swelling. In recent decades, the number of cases of testicular tumours has greatly increased. The most significant predisposing factors are cryptorchidism and some endocrine disorders, especially increased levels of gonadotropins and female sex hormones. Testicular trauma, inguinal hernia, extreme values of body mass index (BMI), high-calorie diet rich in dairy products as well as high social status are also regarded as risk factors. Furthermore, some chromosomal abnormalities like increased number of chromosomes 7, 8. 12, 21 and X, loss of chromosomes 4, 5, 11, 13, 18, or Y, mutation in the gene Xq27; as well as multiplied copy of the gene i(12p) are associated with tumor development. It has been proven that high testosterone levels and regular physical activity may prevent testicular tumours. Since one of the first sign the lesion is often a lump or swelling of the testis and the appearance of abnormal structure in the scrotum routine testicular self-examination seems to be important in early detection. In all suspected cases an immediate ultrasound examination of both testicles is highly recommended. It is also advised to conduct a computerized tomography (CT) and a positron emission tomography (PET) scan for staging of the tumor to select the best mode of treatment. PMID:27137819

  16. Occupational risk factors and voice disorders.

    PubMed

    Vilkman, E

    1996-01-01

    From the point of view of occupational health, the field of voice disorders is very poorly developed as compared, for instance, to the prevention and diagnostics of occupational hearing disorders. In fact, voice disorders have not even been recognized in the field of occupational medicine. Hence, it is obviously very rare in most countries that the voice disorder of a professional voice user, e.g. a teacher, a singer or an actor, is accepted as an occupational disease by insurance companies. However, occupational voice problems do not lack significance from the point of view of the patient. We also know from questionnaires and clinical studies that voice complaints are very common. Another example of job-related health problems, which has proved more successful in terms of its occupational health status, is the repetition strain injury of the elbow, i.e. the "tennis elbow". Its textbook definition could be used as such to describe an occupational voice disorder ("dysphonia professional is"). In the present paper the effects of such risk factors as vocal loading itself, background noise and room acoustics and low relative humidity of the air are discussed. Due to individual factors underlying the development of professional voice disorders, recommendations rather than regulations are called for. There are many simple and even relatively low-cost methods available for the prevention of vocal problems as well as for supporting rehabilitation. PMID:21275584

  17. ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

    PubMed Central

    Frick, Karyn M.

    2009-01-01

    The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

  18. Vascular Basis for Brain Degeneration: Faltering Controls and Risk Factors for Dementia

    PubMed Central

    Kalaria, Raj N.

    2010-01-01

    The integrity of the vascular system is essential for the efficient functioning of the brain. Ageing related structural and functional disturbances in the macro- or microcirculation of the brain make it vulnerable to cognitive dysfunction leading to brain degeneration and dementing illness. Several faltering controls including impairment in autoregulation, neurovascular coupling, blood-brain barrier leakage, decreased cerebrospinal fluid and reduced vascular tone appear responsible for variable degrees of neurodegeneration in old age. There is ample evidence that vascular risk factors are also linked to neurodegenerative processes preceding cognitive decline and dementia. Age is the strongest risk factor for brain degeneration whether it results from vascular or neurodegenerative mechanisms or both. However, several modifiable risks such as cardiovascular disease, hypertension, dyslipidaemia, diabetes and obesity enhance the rate of cognitive decline and increase the risk of Alzheimer’s disease in particular. The ultimate accumulation of brain pathological lesions may be modified by genetic influences such as apoliopoprotein E ε4 allele and the environment. Lifestyle measures that maintain or improve cardiovascular health including consumption of healthy diets, moderate use of alcohol and implementing regular physical exercise are important factors for brain protection. PMID:21091952

  19. Evaluating risk factor assumptions: a simulation-based approach

    PubMed Central

    2011-01-01

    Background Microsimulation models are an important tool for estimating the comparative effectiveness of interventions through prediction of individual-level disease outcomes for a hypothetical population. To estimate the effectiveness of interventions targeted toward high risk groups, the mechanism by which risk factors influence the natural history of disease must be specified. We propose a method for evaluating these risk factor assumptions as part of model-building. Methods We used simulation studies to examine the impact of risk factor assumptions on the relative rate (RR) of colorectal cancer (CRC) incidence and mortality for a cohort with a risk factor compared to a cohort without the risk factor using an extension of the CRC-SPIN model for colorectal cancer. We also compared the impact of changing age at initiation of screening colonoscopy for different risk mechanisms. Results Across CRC-specific risk factor mechanisms, the RR of CRC incidence and mortality decreased (towards one) with increasing age. The rate of change in RRs across age groups depended on both the risk factor mechanism and the strength of the risk factor effect. Increased non-CRC mortality attenuated the effect of CRC-specific risk factors on the RR of CRC when both were present. For each risk factor mechanism, earlier initiation of screening resulted in more life years gained, though the magnitude of life years gained varied across risk mechanisms. Conclusions Simulation studies can provide insight into both the effect of risk factor assumptions on model predictions and the type of data needed to calibrate risk factor models. PMID:21899767

  20. Management of vascular risk factors in the hypertensive patient.

    PubMed

    Taylor, S H

    1990-10-01

    Understanding of the multiple risk factors for premature vascular degeneration is essential for the most effective management of the hypertensive patient. High blood pressure is the most important single predictor of coronary heart disease risk in general clinical practice in the UK. However, hypertension is only a marker of an apparent excess of other risk factors for coronary heart disease among hypertensive patients. The global management of the patient is further complicated for two reasons. First, many of the risk factors are complexly interrelated, either biologically or by lifestyle. Second, the attempted correction of one factor is fraught with the potential for aggravation of the others. The benefits to the coronary and vascular risk profile from lowering blood pressure may be offset, partially or completely, by the aggravation of other risk factors by the antihypertensive drug used. Optimum management of the hypertensive patient can only be achieved when all the risk factors for coronary heart disease in that individual are modified. PMID:2148191

  1. Autophagy and heterophagy dysregulation leads to retinal pigment epithelium dysfunction and development of age-related macular degeneration

    PubMed Central

    Sinha, Debasish; Blasiak, Janusz; Kauppinen, Anu; Veréb, Zoltán; Salminen, Antero; Boulton, Michael E.; Petrovski, Goran

    2013-01-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive eye disease that usually does not lead to complete blindness, but can result in severe loss of central vision. Risk factors for AMD include age, genetics, diet, smoking, oxidative stress and many cardiovascular-associated risk factors. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the retinal pigment epithelium (RPE), is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. To date, there is increasing evidence that constant oxidative stress impairs autophagy and heterophagy, as well as increases protein aggregation and causes inflammasome activation leading to the pathological phenotype of AMD. This review ties together these crucial pathological topics and reflects upon autophagy as a potential therapeutic target in AMD. PMID:23590900

  2. Factors Associated with Sexual Risk-Taking Behaviors among Adolescents.

    ERIC Educational Resources Information Center

    Luster, Tom; Small, Stephen A.

    1994-01-01

    Describes investigation examining factors that distinguish between sexually active adolescents who are at risk for pregnancy and sexually transmitted diseases and those who are at lower risk for these outcomes. Suggests factors associated with sexual risk taking include low GPA, frequent alcohol consumption, and low levels of parental…

  3. Age-related changes in angiogenesis in human dermis.

    PubMed

    Gunin, Andrei G; Petrov, Vadim V; Golubtzova, Natalia N; Vasilieva, Olga V; Kornilova, Natalia K

    2014-07-01

    Present research is aimed to examine the number of dermal blood vessels, vascular endothelial growth factor (VEGF), delta-like ligand 4(Dll4) and Jagged-1 (Jag-1) in dermal blood vessels of human from 20weeks of pregnancy to 85years old. Numbers and proliferative activity of dermal fibroblast-like cells were also examined. Blood vessels were viewed with immunohistochemical staining for von Willebrand factor or CD31. VEGF, Dll4, Jag-1, and proliferating cell nuclear antigen (PCNA) were detected immunohistochemically. Results showed that the numbers of fibroblast-like cells, PCNA positive fibroblast-like cells, von Willebrand factor positive or CD31 positive blood vessels in dermis are dramatically decreased with age. The intensity of immunohistochemical staining for VEGF or Jag-1 in blood vessels of dermis is increased from antenatal to deep old period. The degree of immunohistochemical staining of dermal blood vessels for Dll4 has gone up from 20-40weeks of pregnancy to early life period (0-20years), and further decreased below antenatal values. Age-related decrease in the number of dermal blood vessels is suggested to be due to an impairment of VEGF signaling and to be mediated by Dll4 and Jag-1. It may be supposed that diminishing in blood supply of dermis occurring with age is a cause of a decrease in the number and proliferative pool of dermal fibroblasts. PMID:24768823

  4. Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

    PubMed Central

    GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

    2014-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development

  5. Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder

    PubMed Central

    Castro-Chavira, S.A.; Fernández, T.; Nicolini, H.; Diaz-Cintra, S.; Prado-Alcalá, R.A.

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer’s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  6. The Relationship of Major American Dietary Patterns to Age-related Macular Degeneration

    PubMed Central

    Chiu, Chung-Jung; Chang, Min-Lee; Zhang, Fang Fang; Li, Tricia; Gensler, Gary; Schleicher, Molly; Taylor, Allen

    2014-01-01

    PURPOSE We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. DESIGN Cross-sectional study METHODS 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early AMD (n=4,599), and advanced AMD (n=765) by AREDS AMD Classification System. Food consumption data were collected by a 90-item food frequency questionnaire. RESULTS Two major dietary patterns were identified by factor (principle component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the two patterns by calculating the two factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O=0.74 (95% confidence interval (CI): 0.59–0.91; Ptrend=0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W=1.56 (1.18–2.06; Ptrend=0.01). For advanced AMD, the ORA5O was 0.38 (0.27–0.54; Ptrend<0.0001), and the ORA5W was 3.70 (2.31–5.92; Ptrend<0.0001). CONCLUSIONS Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study. PMID:24792100

  7. Genetic markers in biological fluids for aging-related major neurocognitive disorder.

    PubMed

    Castro-Chavira, S A; Fernandez, T; Nicolini, H; Diaz-Cintra, S; Prado-Alcala, R A

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer' s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  8. Risk factors of jet fuel combustion products.

    PubMed

    Tesseraux, Irene

    2004-04-01

    Air travel is increasing and airports are being newly built or enlarged. Concern is rising about the exposure to toxic combustion products in the population living in the vicinity of large airports. Jet fuels are well characterized regarding their physical and chemical properties. Health effects of fuel vapors and liquid fuel are described after occupational exposure and in animal studies. Rather less is known about combustion products of jet fuels and exposure to those. Aircraft emissions vary with the engine type, the engine load and the fuel. Among jet aircrafts there are differences between civil and military jet engines and their fuels. Combustion of jet fuel results in CO2, H2O, CO, C, NOx, particles and a great number of organic compounds. Among the emitted hydrocarbons (HCs), no compound (indicator) characteristic for jet engines could be detected so far. Jet engines do not seem to be a source of halogenated compounds or heavy metals. They contain, however, various toxicologically relevant compounds including carcinogenic substances. A comparison between organic compounds in the emissions of jet engines and diesel vehicle engines revealed no major differences in the composition. Risk factors of jet engine fuel exhaust can only be named in context of exposure data. Using available monitoring data, the possibilities and limitations for a risk assessment approach for the population living around large airports are presented. The analysis of such data shows that there is an impact on the air quality of the adjacent communities, but this impact does not result in levels higher than those in a typical urban environment. PMID:15093276

  9. Post Traumatic Endophthalmitis: Incidence and Risk Factors

    PubMed Central

    Dehghani, Ali Reza; Rezaei, Leila; Salam, Hasan; Mohammadi, Zahra; Mahboubi, Mohammad

    2014-01-01

    Post traumatic endophthalmitis is an uncommon but severe complication of ocular trauma. We aimed to identify the incidence of post traumatic endophthalmitis and its contributing risk factors in Feiz hospital (Isfahan, Iran) from 2006 until 2010. Medical records of 1042 patients with open globe injury were analyzed and data were collected including age, sex, location of being injured, visual acuity (VA), time from injury to hospitalization and to repair, site of ophthalmic injury and the presence of foreign body. The frequency of post-traumatic endophthalmitis was about 2.1% (N = 22) of all patients. Nine of 22 cases with endophthalmitis were under 8 years. The visual acuity at the time of admission was seen to be contributed to high rate of endophthalmitis. Intraocular foreign body was detected in 139 patients; and the rate of endophthalmitis was 5% among these patients. Statistical analysis showed significant relationship between presence of foreign body and higher rate of endophthalmitis. Also, duration of hospitalization was significantly different between two study groups (P = 0.019). There were no significant differences between two groups in terms of other studied variables. Patients with low age, low visual acuity at admission, presence of intraocular foreign body and long duration of hospital stay had a higher risk of endophthalmitis after the repair of the globe. Compared to the reports of other large institutions, we can attribute the low incidence rate of endophthalmitis in our institution to the early use of systemic antibiotics such as gentamycin and cephalosporins in the first hour of hospitalization until discharge. PMID:25363107

  10. Risk factors for ocular toxoplasmosis in Brazil.

    PubMed

    Ferreira, A I C; De Mattos, C C Brandão; Frederico, F B; Meira, C S; Almeida, G C; Nakashima, F; Bernardo, C R; Pereira-Chioccola, V L; De Mattos, L C

    2014-01-01

    The aim of this study was to investigate risk factors for ocular toxoplasmosis (OT) in patients who received medical attention at a public health service. Three hundred and forty-nine consecutive patients, treated in the Outpatient Eye Clinic of Hospital de Base, São José do Rio Preto, São Paulo state, Brazil, were enrolled in this study. After an eye examination, enzyme-linked immunosorbent assay (ELISA) was used to determine anti-Toxoplasma gondii antibodies. The results showed that 25.5% of the patients were seronegative and 74.5% were seropositive for IgG anti-T. gondii antibodies; of these 27.3% had OT and 72.7% had other ocular diseases (OOD). The presence of cats or dogs [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.24-3.98, P = 0.009] and consumption of raw or undercooked meat (OR 1.77, 95% CI 1.05-2.98, P = 0.03) were associated with infection but not with the development of OT. Age (OT 48.2 ± 21.2 years vs. OOD: 69.5 ± 14.7 years, P < 0.0001) and the low level of schooling/literacy (OT vs. OOD: OR 0.414, 95% CI 0.2231-0.7692, P = 0.007) were associated with OT. The presence of dogs and cats as well as eating raw/undercooked meat increases the risk of infection, but is not associated with the development of OT. PMID:23507508

  11. Association between CFH Y402H Polymorphism and Age Related Macular Degeneration in North Indian Cohort

    PubMed Central

    Gupta, Amod; Prabhakar, Sudesh; Singh, Ramandeep; Sharma, Suresh Kumar; Chen, Wei

    2013-01-01

    The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels. PMID:23922956

  12. Influence of Age-Related Versus Non-Age-Related Renal Dysfunctionon Survival in Patients with Left Ventricular Dysfunction

    PubMed Central

    Testani, Jeffrey M.; Brisco, Meredith A.; Han, Gang; Laur, Olga; Kula, Alexander J.; Cheng, Susan J.; Tang, W. H. Wilson; Parikh, Chirag R.

    2013-01-01

    Normal aging results in a predictable decline in glomerular filtration rate (GFR) and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age related declines in estimated GFR (eGFR) carry the same prognostic importance as disease attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337). The primary analysis focused on determining if the eGFR mortality relationship differed by the extent the eGFR was consistent with normal ageing. Mean eGFR was 65.7 ± 19.0ml/min/1.73m2. Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73m2 per year (95% CI 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted HR=1.0 per 10 ml/min/1.73m2, 95% CI 0.97–1.1, p=0.53) whereas a disease attributable decrease in eGFR above the median carried significant risk (adjusted HR=2.8, 95% CI 1.6–4.7, p<0.001). In conclusion, in the setting of LV dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis. PMID:24216124

  13. [Depression in Patients with Age-Related Macular Degeneration].

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. PMID:26572116

  14. Whole exome sequencing of extreme age-related macular degeneration phenotypes

    PubMed Central

    Sardell, Rebecca J.; Bailey, Jessica N Cooke; Courtenay, Monique D.; Whitehead, Patrice; Laux, Reneé A.; Adams, Larry D.; Fortun, Jorge A.; Brantley, Milam A.; Kovach, Jaclyn L.; Schwartz, Stephen G.; Agarwal, Anita; Scott, William K.; Haines, Jonathan L.

    2016-01-01

    Purpose Demographic, environmental, and genetic risk factors for age-related macular degeneration (AMD) have been identified; however, a substantial portion of the variance in AMD disease risk and heritability remains unexplained. To identify AMD risk variants and generate hypotheses for future studies, we performed whole exome sequencing for 75 individuals whose phenotype was not well predicted by their genotype at known risk loci. We hypothesized that these phenotypically extreme individuals were more likely to carry rare risk or protective variants with large effect sizes. Methods A genetic risk score was calculated in a case–control set of 864 individuals (467 AMD cases, 397 controls) based on 19 common (≥1% minor allele frequency, MAF) single nucleotide variants previously associated with the risk of advanced AMD in a large meta-analysis of advanced cases and controls. We then selected for sequencing 39 cases with bilateral choroidal neovascularization with the lowest genetic risk scores to detect risk variants and 36 unaffected controls with the highest genetic risk score to detect protective variants. After minimizing the influence of 19 common genetic risk loci on case-control status, we targeted single variants of large effect and the aggregate effect of weaker variants within genes and pathways. Single variant tests were conducted on all variants, while gene-based and pathway analyses were conducted on three subsets of data: 1) rare (≤1% MAF in the European population) stop, splice, or damaging missense variants, 2) all rare variants, and 3) all variants. All analyses controlled for the effects of age and sex. Results No variant, gene, or pathway outside regions known to be associated with risk for advanced AMD reached genome-wide significance. However, we identified several variants with substantial differences in allele frequency between cases and controls with strong additive effects on affection status after controlling for age and sex

  15. Lifestyle decreases risk factors for cardiovascular diseases.

    PubMed

    Slavícek, Jaroslav; Kittnar, Otomar; Fraser, Gary E; Medová, Eva; Konecná, Jana; Zizka, Robert; Dohnalová, Alena; Novák, Vladimir

    2008-12-01

    The morbidity and mortality of cardiovascular diseases is high in the developed countries. The lifestyle changes are capable to decrease it by 50%. The aim of the present study was to measure the parameters of some risk factors before and after a one-week NEW START rehabilitative retreat. 1349 volunteers, 320 men, 1029 woman, mean age 51 +/- 14.5 (SD) years participated in 30 rehabilitative retreats from 1999-2006 in the Czech Republic, using a low-fat, low-energy, lacto-ovo-vegetarian diet and exercise, in a stress-free environment. Body weight, height, BMI, blood pressure, heart rate, serum cholesterol and blood glucose were measured. Body weight decreased in 1223 measured persons from 71.2 +/- 14.38 (SD) to 70.6 +/- 14.02 kg (p<0.0001), BMI (1,046 measured persons) from 25.1 +/- 4.60 (SD) to 24.8+4.49 (SD) kg/m2 (p<0.0001), systolic blood pressure (1,218 persons) from 129.8 +/- 23.02 (SD) to 123.8 +/- 21.52 (SD) mmHg (p<0.0001), diastolic blood pressure (1210 persons) from 79.8 +/- 12.7 (SD) to 77.5 +/- 11.6 (SD) mmHg (p<0.0001), serum cholesterol (998 persons) from 4.86 +/- 0.95 (SD) to 4.32 +/- 0.77 (SD) mmol (p<0.0001), blood glucose (544 persons) from 4.31 +/- 1.59 (SD) to 3.88 +/- 1.33 (SD) mmol (p<0.0001). Heart rate was not significantly decreased. The parameters were lower in lacto-ovo vegetarians and Seventh-day Adventists than in controls who never observed the diet and avail the lifestyle programs. The parameters were nonsignificantly changed one year after finishing the retreat in the sample of 68 persons showing the positive effect of retreats. Our results showed, that the intake of a low-fat, low-energy diet, over the course of one week in a stress-free environment, had positive impact on the risk factors of cardiovascular diseases. PMID:19256282

  16. Fighting Gum Disease: Risk Factors, Treatment and Research

    MedlinePlus

    ... Feature: Fighting Gum Disease Risk Factors, Treatment and Research Past Issues / Fall 2010 Table of Contents Risk ... out whether it offers this service. Latest NIH Research Researchers supported by the National Institute of Dental ...

  17. What Are the Risk Factors for Myelodysplastic Syndromes?

    MedlinePlus

    ... surviving an atomic bomb blast or nuclear reactor accident) increases the risk of developing MDS. Long-term ... Myelodysplastic Syndrome? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Myelodysplastic Syndrome Talking With ...

  18. What Are the Risk Factors for Chronic Myeloid Leukemia?

    MedlinePlus

    ... of an atomic bomb blast or nuclear reactor accident) increases the risk of getting CML Age : The ... Myeloid (CML)? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating Leukemia - Chronic Myeloid (CML) ...

  19. Heart Disease Risk Factors | NIH MedlinePlus the Magazine

    MedlinePlus

    ... JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table of Contents You Can Reduce Your Risk Certain traits, conditions, or habits may raise your ...