Genetic association studies of multiple populations investigate a wider range of risk alleles than studies of a single ethnic group. In this study, we developed a multiethnic tagging strategy, ...exploiting differences in linkage disequilibrium (LD) structure between populations, to comprehensively capture common genetic variation across 60 genes spanning multiple DNA repair pathways, in five racial/ethnic populations. Over 2600 SNPs were genotyped in each population and single- and multi-marker predictors of common alleles were selected to capture the LD patterns specific to each group. Coding variants (n = 211) were genotyped to test whether combinations of putative functional variants in DNA repair pathway genes could have cumulative effects on risk. Tests of association were conducted in a multiethnic breast cancer study (2093 cases and 2303 controls), with validation of the top allelic associations (P ≤ 0.01) performed in additional studies of 6483 cases and 7309 controls. A variant in the FANCA gene (rs1061646, 0.15–0.68 frequency across populations) was associated with risk in the initial study (P = 0.0052), and in the replication studies (P = 0.032). In a combined analysis (8556 cases and 9605 controls), this SNP yielded an 8% increase in risk per allele. Combinations of coding variants in these genes were not associated with breast cancer and together, these data suggest that common variation in these DNA repair pathway genes are not strongly associated with breast cancer risk. The methods utilized in this study, applied to multiple populations, provide a framework for testing in association studies in diverse populations.
Summary
Background Psoriasis has been linked to cardiovascular comorbidities in cross‐sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease ...(CVD) is limited.
Objectives To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD.
Methods Participants (n = 96 008) were included from the Nurses’ Health Study II, and followed for 18 years. Information on physician‐diagnosed psoriasis was obtained by self‐report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self‐reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events nonfatal myocardial infarction (MI) and nonfatal stroke, ascertained by biennial questionnaires and confirmed.
Results During 1 709 069 person‐years of follow‐up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate‐adjusted hazard ratio (HR) of nonfatal CVD, 1·55 95% confidence interval (CI): 1·04–2·31. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01–2·84) and 1·45 (95% CI: 0·80–2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31–3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85–6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21–8·75) and 3·09 (95% CI: 1·15–8·29), respectively.
Conclusions Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.
Daily concentrations of lead (Pb) were determined for PM
2.5 samples collected from an urban location in Xi’an, China from 2007 to 2009 to assess the effects of the phasing out of leaded gasoline in ...2000. The Pb concentrations (annual average: 0.306 μg m
−3, range: below detection limit to 2.631 μg m
−3) have declined after the phasing out of leaded gasoline, but the concentrations were still higher than those reported in many other cities. Seasonal variations of Pb were significant, with high concentrations in winter, presumably due to the burning of coal, and low concentrations in summer, due to a deep mixed layer and scavenging of aerosols by precipitation. Correlation analyses and enrichment factor calculations both indicated that anthropogenic sources had a large influence on atmospheric Pb. The lead isotope ratios were low in winter (the average
207Pb/
206Pb ratio was 0.843 ± 0.032;
208Pb/
206Pb was 1.908 ± 0.058) and high in summer (
207Pb/
206Pb was 0.860 ± 0.032;
208Pb/
206Pb was 2.039 ± 0.057), suggesting that coal combustion was the major Pb source in winter and vehicular emission was the major Pb source in summer. Positive Matrix Factorization receptor model indicated that there were five major sources for Pb in PM
2.5. Coal combustion was the major contributor, accounting for 39.0% PM
2.5 mass, followed by vehicular emissions (30.4%). Other contributors included 17.8% from industrial emissions, 11.6% from biomass burning, and 1.2% from fugitive dust.
► Pb concentrations (average: 0.306 μg m
−3 during 2007–2009) have declined after the phasing out of leaded gasoline. ► Pb concentrations in Xi’an are still higher than those reported in many other cities. ► Coal combustion was the strongest source for PM
2.5 Mass (39.0%).
To assess the usefulness of flexible covered metallic stents in the palliation of malignant obstruction of the gastric outlet and duodenum.
Twenty-four consecutive patients with malignant obstruction ...of the gastric outlet (n = 22) or duodenum (n = 2) underwent palliative treatment with self-expandable flexible covered metallic stents. Fourteen patients had advanced gastric carcinoma at the antrum and/or pylorus, and eight had obstruction at the anastomosis site of previous gastrojejunostomy. Complications and clinical status were investigated during the study period.
The technical success rate was 75% (18 of 24 patients). Twenty-one stents were placed in 18 patients by using an introducer 6 (n = 7) or 8 mm (n = 14) in diameter. The mean follow-up period was 3.4 months (range, 1 week to 9 months). Symptoms improved in 12 (67%) patients after the procedure. There was no change in symptoms in five and a decrease in one. Twelve patients died during the follow-up period (mean survival, 4.3 months). The complication rate was 25% (six of 24 patients), including stent migration (n = 5) and fracture (n = 3).
Flexible covered metallic stent placement can be useful for palliation in patients with malignant obstruction of the gastric outlet or duodenum.
The purpose of this study was to investigate the neuroprotective potential of submicron (milled) and blended Lycium barbarum (LB) in glaucomatous retinal neuropathy using a rat model of high ...intraocular pressure (HIOP) induced retinal ischemia. The rats were treated with 500, 250, 100 mg/kg LB (submicron or blended form) orally once daily for 56 days respectively after 1 week of retinal ischemia induction. We conducted electroretinography (ERG), histopathological analysis in retina and antioxidative level assays, such as total glutathione (GSH (glutathione) + reduced glutathione) + GSSH (glutathione disulfide), catalase activity, SOD (superoxide dismutase) activity, and lipid peroxidant malondialdehyde (MDA) in the retina and plasma of test rats. The results indicated that the amplitudes of a and b wave of ERG were preserved in rats treated with submicron and blended LB groups, the best protective effect on ERG b wave amplitudes was observed at the dosage of 250 mg/kg of both forms of LB. Retinal thickness was best preserved, particularly significant in the retinal inner nuclear layer in submicron 250 mg/kg LB group. The levels of antioxidant GSSH+GSH, SOD and catalase activity in the retina were higher in blended 500 mg/kg and submicron 250 mg/kg groups than other groups, while the MDA level was lower in submicron LB groups than that in blended LB and non-LB IR group. In the plasma, there was no significant difference in the levels of GSSH+GSH and catalase activity between treated groups, but higher levels of SOD and lower levels of MDA were observed in 250 mg/kg submicron and 500 mg/kg submicron LB groups than the blended LB and non-LB IR groups. Generally better antioxidative effects were observed in the submicron LB than blended LB among treated groups, especially the 250 mg/kg submicron LB, providing good retinal neuroprotection by preserving retinal structure and function with improved antioxidative capacity. The submicron LB may have clinical implication as an adjuvant therapy of oxidative stress and retinal damage caused by HIOP induced retinal ischemia and reperfusion injury.
Chronic obstructive pulmonary disease (COPD) is considered to be caused in part by smoking-induced inflammation, but it is unknown which inflammatory cells within the small airways are associated ...with the obstruction. We investigated the inflammatory infiltrate in the small airways of 16 current or ex-smokers with COPD (FEV1 < or = 75% predicted) and 15 without COPD (FEV1 > or = 85% predicted) in pneumectomy specimens that were removed for lung cancer. Mast cells, macrophages, neutrophils, eosinophils, T cells, and B cells were identified using immunohistochemistry on formalin-fixed, paraffin-embedded specimens. These cells were quantified in the epithelium and the remainder of the airway wall. The number of mast cells and macrophages in the epithelium, but not in the remainder of the airway wall, was significantly increased in patients with COPD. Neutrophil and T cell numbers did not differ between the groups. Only few B cells and eosinophils were present in both groups. Smoking history, perioperative steroid usage, tumor localization, or reversibility in the FEV1 to salbutamol could not account for the observed differences. We conclude that the number of epithelial mast cells and macrophages is increased in the bronchioli in smokers with airflow limitation, suggesting a role in development of COPD.
Daily PM
2.5 and water-soluble inorganic ions (Na
+, NH
4
+, K
+, Mg
2+, Ca
2+, Cl
−, NO
3
− and SO
4
2−) were collected in Xi'an (34.23°N, 108.88°E), China from March 2006 to March 2007. PM
2.5 was ...collected using battery-powered mini-volume samplers. And the ions were determined by ion chromatography from the measured aerosol mass. The annual average mass concentration of PM
2.5 was found to be 194.1
±
78.6
μg
m
−
3
, which exceeded substantially the international guidelines for health concerns. The seasonal average mass concentration of PM
2.5 was highest in winter (266.8
μg
m
−
3
) and lowest in summer (138.6
μg
m
−
3
). The three highest abundant ions were SO
4
2−, NO
3
−, and NH
4
+, with average concentrations of 35.6
±
19.5
μg
m
−
3
, 16.4
±
10.1
μg
m
−
3
, and 11.4
±
6.8
μg
m
−
3
, which were accounted for 18.7%, 8.0%, and 5.7% of the PM
2.5 mass, respectively. The major ions were in the species of (NH
4)
2SO
4, NH
4HSO
4 and NH
4NO
3, and their concentrations were highest in winter, due to high coal combustion. The concentrations of Ca
2+ were higher in spring than other seasons, due to the higher mineral dust concentrations. Ca
2+ was strongly correlated with CO
3
2−, which was calculated as the difference in the measured cations minus anions. Ion balance calculations indicate that the PM
2.5 was acidic, and this result is consistent with the measurement of pH values. Sulfur oxidation ratio was higher in summer and autumn, which implies that the formation of secondary sulfate-rich particles is favored by warm and relatively moist weather. Nitrogen oxidation ratio was highest in autumn.
► Coal combustion has heavy impact on the variations of water-soluble ions. ► PM
2.5 in non-spring was acidic, while the aerosol was less acidic and possibly even alkaline in spring due to the buffering effects of mineral dust. ► Relationship between CO
3
2- and Ca
2+ implies that Ca
2CO
3 was the major form for the aerosol carbonate.
The p.R713Q variant of the semaphorin-4a-encoding gene, SEMA4a, has been reported to cause autosomal dominant retinitis pigmentosa. Here we show three families with retinal degeneration in which ...unaffected family members are either homozygous or heterozygous for the variant. The p.R713Q variant in SEMA4A is insufficient to cause either autosomal recessive or autosomal dominant retinitis pigmentosa and is unlikely to be pathogenic.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In food ink systems in which the particles are dispersed in a hydrocolloid matrix, the source of the particles and the particle content are the main factors affecting the printability and rheological ...properties of the system. In this study, different contents (10% and 30% w/w) of vegetable (broccoli, spinach, or carrot) powders were added to hydrocolloid matrices with different hydration properties, and their influence on the printability and rheological properties was investigated. At low powder contents (10%), slight differences in the printability and rheological values were observed between the different vegetable sources in all hydrocolloids. When the powder content was increased to 30%, the hydrocolloid with the lowest water hydration capacity, hydroxypropyl methylcellulose, showed the greatest differences in rheology and printability when different vegetable sources were used. Xanthan gum, with its higher water hydration capacity, inhibited the swelling of the particles, thus minimizing the increase in the rheological values at high volume fractions of powder and reducing the differences in printability between different vegetable sources. Confocal laser scanning microscopy analysis of the vegetable inks showed that xanthan gum inhibited swelling of the particles regardless of the vegetable powder source. The mixtures using xanthan gum could be smoothly extruded from the nozzle due to their low extruded hardness (2.96 ± 0.23 to 3.46 ± 0.16 kg), and the resulting objects showed high resolution without collapse over time.
Practical Application
The powder‐based texturization technology introduced in this study provides a standardized method of preparing food ink that can be universally applied to all food materials that can be powdered. In addition, the present invention can be applied to a 3D printing technique in which a powder and a hydrocolloid matrix are independently stored and mixed immediately before printing. This technique can minimize the inherent rheological differences between formulations with different food sources and compositions.
PDF
