BackgroundFerritin positively associates with serum urate and an interventional study suggests that iron has a role in triggering gout flares. The objective of this study was to further explore the relationship between iron/ferritin and urate/gout.MethodsEuropean (100 cases, 60 controls) and Polynesian (100 cases, 60 controls) New Zealand (NZ) males and 189 US male cases and 60 male controls participated. The 10,727 participants without gout were from the Jackson Heart (JHS; African American = 1260) and NHANES III (European = 5112; African American = 4355) studies. Regression analyses were adjusted for age, sex, body mass index and C-reactive protein. To test for a causal relationship between ferritin and urate, bidirectional two-sample Mendelian randomization analysis was performed.ResultsSerum ferritin positively associated with gout in NZ Polynesian (OR (per 10 ng ml− 1 increase) = 1.03, p = 1.8E–03) and US (OR = 1.11, p = 7.4E–06) data sets but not in NZ European (OR = 1.00, p = 0.84) data sets. Ferritin positively associated with urate in NZ Polynesian (β (mg dl− 1) = 0.014, p = 2.5E–04), JHS (β = 0.009, p = 3.2E–05) and NHANES III (European β = 0.007, p = 5.1E–11; African American β = 0.011, p = 2.1E–16) data sets but not in NZ European (β = 0.009, p = 0.31) or US (β = 0.041, p = 0.15) gout data sets. Ferritin positively associated with the frequency of gout flares in two of the gout data sets. By Mendelian randomization analysis a one standard deviation unit increase in iron and ferritin was, respectively, associated with 0.11 (p = 8E–04) and 0.19 mg dl− 1 (p = 2E–04) increases in serum urate. There was no evidence for a causal effect of urate on iron/ferritin.ConclusionsThese data replicate the association of ferritin with serum urate. Increased ferritin levels associated with gout and flare frequency. There was evidence of a causal effect of iron and ferritin on urate.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1668-y) contains supplementary material, which is available to authorized users.

BackgroundIncreased coffee intake is associated with reduced serum urate concentrations and lower risk of gout. Specific alleles of the GCKR, ABCG2, MLXIPL, and CYP1A2 genes have been associated with both reduced coffee intake and increased serum urate in separate genome-wide association studies (GWAS). The aim of this study was to determine whether these single nucleotide polymorphisms (SNPs) influence the risk of gout through their effects on coffee consumption.MethodsThis research was conducted using the UK Biobank Resource. Data were available for 130,966 European participants aged 40–69 years. Gout status and coffee intake were tested for association with four urate-associated SNPs: GCKR (rs1260326), ABCG2 (rs2231142), MLXIPL (rs1178977), and CYP1A2 (rs2472297). Multiple regression and path analysis were used to examine whether coffee consumption mediated the effect of the SNPs on gout risk.ResultsCoffee consumption was inversely associated with gout (multivariate adjusted odds ratio (95% confidence interval (CI)) for any coffee consumption 0.75 (0.67–0.84, P = 9 × 10−7)). There was also evidence of a dose-effect with multivariate adjusted odds ratio (95% CI) per cup consumed per day of 0.85 (0.82–0.87, P = 9 × 10−32). The urate-increasing GCKR, ABCG2, MLXIPL, and CYP1A2 alleles were associated with reduced daily coffee consumption, with the strongest associations for CYP1A2 (beta −0.30, P = 8 × 10−40), and MLXIPL (beta −0.17, P = 3 × 10−8), and weaker associations for GCKR (beta −0.07, P = 3 × 10−10) and ABCG2 (beta −0.09, P = 2 × 10−9). The urate-increasing GCKR and ABCG2 alleles were associated with gout (multivariate adjusted p < 5 × 10−8 for both), but the urate-increasing MLXIPL and CYP1A2 alleles were not. In mediation analysis, the direct effects of GCKR and ABCG2 accounted for most of the total effect on gout risk, with much smaller indirect effects mediated by coffee consumption.ConclusionCoffee consumption is inversely associated with risk of gout. Although alleles at several SNPs associate with both lower coffee consumption and higher risk of gout, these SNPs largely influence gout risk directly, rather than indirectly through effects on coffee consumption.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1629-5) contains supplementary material, which is available to authorized users.

Background Gout is predicted by a number of comorbidities and lifestyle factors. We aimed to identify discrete phenotype clusters of these factors in a Swedish population-based health survey. In these clusters, we calculated and compared the incidence and relative risk of gout. Methods Cluster analyses were performed to group variables with close proximity and to obtain homogenous clusters of individuals (n = 22,057) in the Malmö Preventive Project (MPP) cohort. Variables clustered included obesity, kidney dysfunction, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), dyslipidemia, pulmonary dysfunction (PD), smoking, and the use of diuretics. Incidence rates and hazard ratios (HRs) for gout, adjusted for age and sex, were computed for each cluster. Results Five clusters (C1–C5) were identified. Cluster C1 (n = 16,063) was characterized by few comorbidities. All participants in C2 (n = 750) had kidney dysfunction (100%), and none had CVD. In C3 (n = 528), 100% had CVD and most participants were smokers (74%). C4 (n = 3673) had the greatest fractions of obesity (34%) and dyslipidemia (74%). In C5 (n = 1043), proportions with DM (51%), hypertension (54%), and diuretics (52%) were highest. C1 was by far the most common in the population (73%), followed by C4 (17%). These two pathways included 86% of incident gout cases. The four smaller clusters (C2–C5) had higher incidence rates and a 2- to 3-fold increased risk for incident gout. Conclusions Five distinct clusters based on gout-related comorbidities and lifestyle factors were identified. Most incident gout cases occurred in the cluster of few comorbidities, and the four comorbidity pathways had overall a modest influence on the incidence of gout.

Introduction The relationship between urate and biomarkers for Alzheimer's disease (AD) pathophysiology has not been investigated. Methods We examined whether serum concentration of urate was associated with cerebrospinal fluid biomarkers, amyloid beta (Aβ) 42 , Aβ 40 , phosphorylated tau (p‐tau), total tau (t‐tau), neurofilament light (NfL), and Aβ 42 /Aβ 40 ratio, in cognitively unimpaired 70‐year‐old individuals from Gothenburg, Sweden. We also evaluated whether possible associations were modulated by the apolipoprotein E ( APOE ) ε4 allele. Results Serum urate was positively associated with Aβ 42 in males (β = 0.55 pg/mL, P = .04). There was a positive urate– APOE ε4 interaction (1.24 pg/mL, P interaction = .02) in relation to Aβ 42 association. The positive urate and Aβ 42 association strengthened in male APOE ε4 carriers (β = 1.28 pg/mL, P = .01). Discussion The positive association between urate and Aβ 42 in cognitively healthy men may suggest a protective effect of urate against deposition of amyloid protein in the brain parenchyma, and in the longer term, maybe against AD dementia.

The Arg64 allele of variant rs4994 (Trp64Arg) in the β3-adrenergic receptor gene has been associated with increased serum urate and risk of gout. Our objective was to investigate the relationship of rs4994 with serum urate and gout in New Zealand European, Māori and Pacific subjects. A total of 1730 clinically ascertained gout cases and 2145 controls were genotyped for rs4994 by Taqman®. Māori and Pacific subjects were subdivided into Eastern Polynesian (EP) and Western Polynesian (WP) sample sets. Publicly available genotype data from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study were utilized for serum urate association analysis. Multivariate logistic and linear regression adjusted for potential confounders was carried out using R version 2.15.2. No significant association of the minor Arg64 (G) allele of rs4994 with gout was found in the combined Polynesian cohorts (OR = 0.98, P = 0.88), although there was evidence, after adjustment for renal disease, for association in both the WP (OR = 0.53, P = 0.03) and the lower Polynesian ancestry EP sample sets (OR = 1.86, P = 0.05). There was no evidence for association with gout in the European sample set (OR = 1.11, P = 0.57). However, the Arg64 allele was positively associated with urate in the WP data set (β = 0.036, P = 0.004, PCorrected = 0.032). Association of the Arg64 variant with increased urate in the WP sample set was consistent with the previous literature, although the protective effect of this variant with gout in WP was inconsistent. This association provides an etiological link between metabolic syndrome components and urate homeostasis.

Some well defined connectivity topological indices are Randic index, atom-bond connectivity index, geometric-arithmetic index and Shigehalli & Kanabur indices, brought into light by M. Randic, Estrada et al, Vukicevic et al and V. S. Shigehalli, in their respective research articles.Topological indices preserve the symmetry of molecular structures and provide a mathematical formulation to predict their properties like boiling points, viscosity and the radius of gyrations, 1 mainly their study gets a cover under the category of physical chemistry. Due to its mathematical nature, this idea has caught the attention of many chemists. It has also been reported that these indices are useful in the study of anti-inflammatory activities of certain chemical instances. In this paper, we shall calculate these topological indices of an infinite class of octagonal tilling structures OT [m, n], which is a molecular graph of a semiconductor allotrope consisting of octagons and rectangles, for all possible values of the parameters m and n. We shall also calculate Shigehalli & Kanabur indices of infinite structure of the titania TiO 2 nanotubes.

Background: Pleural effusion is one of the commonly seen respiratory conditions in India with approximately 1 million people being diagnosed each year. Twenty to forty percent of hospitalized patients with bacterial pneumonia develop pleural effusion. In India unlike western countries, tuberculosis pleura effusion is common. The pleural cavity is involved in approximately 5% of all patients with tuberculosis. Since there was no literature regarding the effectiveness chest mobility exercise with staked breathing or chest mobility exercises with incentive spirometery in pleural effusion. There was a need to find out as to which approach are the best ones to implement. Objective: To compare the efficacy of chest mobility exercise with stacked breathing versus chest mobility exercise with incentive spirometery on chest expansion in patients with pleural effusion. Materials and Method: 20 patients with pleural effusion were selected by easy sampling and randomly assigned into two groups (10 patients each groups). Group A received chest mobility exercises and intensive spirometery and group B received chest mobility exercises and stacked breathing. Both groups were instructed to perform the intervention 3 time per day, 8 to 10 time per session for one week. Chest expansion was measured by thoracic flow cytometry before and after one week of intervention. Result: In group A chest expansion increase from 2.68 to 2.87 which was statistically significant (P value < 0.0023). In Group B the chest expansion increases from 2.94 to 3.09 which was not statistically significant (P value < 0.216). Conclusion: It was concluded from the result that both chest mobility exercises with intensive spirometery and chest mobility exercise with stacked breathing are equally effective in improving the chest expansion in subject with pleural effusion. KEY WORDS: Pleural effusion, Chest mobility exercises, Incentive Spirometry, Stacked breathing, Thoracic flow cytometry.

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.