Hypoxia-inducible factor-1α gene polymorphisms and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The results from the published studies on the association between <it>hypoxia-inducible factor -1α </it>(HIF-1α) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between <it>HIF-1α </it>1772 C/T and 1790 G/A polymorphisms and cancer.</p> <p>Methods</p> <p>The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.</p> <p>Results</p> <p>For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P_{heterogeneity}< 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P_{heterogeneity}= 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P_{heterogeneity}= 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P_{heterogeneity}= 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P_{heterogeneity}= 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P_{heterogeneity}= 0.41, respectively. The frequency of the <it>HIF-1α </it>1790 A allele was very low and only two studies were included in the breast cancer subgroup.</p> <p>Conclusions</p> <p>Our meta-analysis suggests that the <it>HIF-1α </it>1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.</p

Prioritising surveillance for alien organisms transported as stowaways on ships travelling to South Africa

The global shipping network facilitates the transportation and introduction of marine and terrestrial organisms to regions where they are not native, and some of these organisms become invasive. South Africa was used as a case study to evaluate the potential for shipping to contribute to the introduction and establishment of marine and terrestrial alien species (i.e. establishment debt) and to assess how this varies across shipping routes and seasons. As a proxy for the number of species introduced (i.e. 'colonisation pressure') shipping movement data were used to determine, for each season, the number of ships that visited South African ports from foreign ports and the number of days travelled between ports. Seasonal marine and terrestrial environmental similarity between South African and foreign ports was then used to estimate the likelihood that introduced species would establish. These data were used to determine the seasonal relative contribution of shipping routes to South Africa's marine and terrestrial establishment debt. Additionally, distribution data were used to identify marine and terrestrial species that are known to be invasive elsewhere and which might be introduced to each South African port through shipping routes that have a high relative contribution to establishment debt. Shipping routes from Asian ports, especially Singapore, have a particularly high relative contribution to South Africa's establishment debt, while among South African ports, Durban has the highest risk of being invaded. There was seasonal variation in the shipping routes that have a high relative contribution to the establishment debt of the South African ports. The presented method provides a simple way to prioritise surveillance effort and our results indicate that, for South Africa, port-specific prevention strategies should be developed, a large portion of the available resources should be allocated to Durban, and seasonal variations and their consequences for prevention strategies should be explored further. (Résumé d'auteur

Level and course of FEV1 in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

<p>Abstract</p> <p>Background</p> <p>The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and <it>Nfe2l2</it>-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV₁) in the general population.</p> <p>Methods</p> <p>Five <it>NFE2L2 </it>and three <it>KEAP1 </it>tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV₁measurements during 3 surveys, respectively 7 FEV₁measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV₁measurements.</p> <p>Results</p> <p>In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in <it>KEAP1 </it>was associated with a higher FEV₁level (p = 0.02 for an additive effect), and SNP rs2364723 in <it>NFE2L2 </it>was associated with a lower FEV₁level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of <it>KEAP1 </it>or <it>NFE2L2 </it>SNPs with FEV₁decline was observed.</p> <p>Conclusion</p> <p>This is the first genetic study on variations in key antioxidant transcriptional regulators <it>KEAP1 </it>and <it>NFE2L2 </it>and lung function in a general population. It identified 2 SNPs in <it>NFE2L2 </it>and <it>KEAP1 </it>which affect the level of FEV₁in the general population. It additionally shows that <it>NFE2L2 </it>and <it>KEAP1 </it>variations are unlikely to play a role in the longitudinal course of FEV₁in the general population.</p

Non prescribed sale of antibiotics in Riyadh, Saudi Arabia: A Cross Sectional Study

Background Antibiotics sales without medical prescriptions are increasingly recognized as sources of antimicrobial misuse that can exacerbate the global burden of antibiotic resistance. We aimed to determine the percentage of pharmacies who sell antibiotics without medical prescriptions, examining the potential associated risks of such practice in Riyadh, Saudi Arabia, by simulation of different clinical scenarios. Methods A cross sectional study of a quasi-random sample of pharmacies stratified by the five regions of Riyadh. Each pharmacy was visited once by two investigators who simulated having a relative with a specific clinical illness (sore throat, acute bronchitis, otitis media, acute sinusitis, diarrhea, and urinary tract infection (UTI) in childbearing aged women). Results A total of 327 pharmacies were visited. Antibiotics were dispensed without a medical prescription in 244 (77.6%) of 327, of which 231 (95%) were dispensed without a patient request. Simulated cases of sore throat and diarrhea resulted in an antibiotic being dispensed in (90%) of encounters, followed by UTI (75%), acute bronchitis (73%), otitis media (51%) and acute sinusitis (40%). Metronidazole (89%) and ciprofloxacin (86%) were commonly given for diarrhea and UTI, respectively, whereas amoxicillin/clavulanate was dispensed (51%) for the other simulated cases. None of the pharmacists asked about antibiotic allergy history or provided information about drug interactions. Only 23% asked about pregnancy status when dispensing antibiotics for UTI-simulated cases. Conclusions We observed that an antibiotic could be obtained in Riyadh without a medical prescription or an evidence-based indication with associated potential clinical risks. Strict enforcement and adherence to existing regulations are warranted

Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization

Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate

Comparison of Storage Conditions for Human Vaginal Microbiome Studies

BACKGROUND: The effect of storage conditions on the microbiome and metabolite composition of human biological samples has not been thoroughly investigated as a potential source of bias. We evaluated the effect of two common storage conditions used in clinical trials on the bacterial and metabolite composition of the vaginal microbiota using pyrosequencing of barcoded 16S rRNA gene sequencing and (1)H-NMR analyses. METHODOLOGY/PRINCIPAL FINDINGS: Eight women were enrolled and four mid-vaginal swabs were collected by a physician from each woman. The samples were either processed immediately, stored at -80°C for 4 weeks or at -20°C for 1 week followed by transfer to -80°C for another 4 weeks prior to analysis. Statistical methods, including Kolmogorovo-Smirnov and Wilcoxon tests, were performed to evaluate the differences in vaginal bacterial community composition and metabolites between samples stored under different conditions. The results showed that there were no significant differences between samples processed immediately after collection or stored for varying durations. (1)H-NMR analysis of the small molecule metabolites in vaginal secretions indicated that high levels of lactic acid were associated with Lactobacillus-dominated communities. Relative abundance of lactic acid did not appear to correlate with relative abundance of individual Lactobacillus sp. in this limited sample, although lower levels of lactic acid were observed when L. gasseri was dominant, indicating differences in metabolic output of seemingly similar communities. CONCLUSIONS/SIGNIFICANCE: These findings benefit large-scale, field-based microbiome and metabolomic studies of the vaginal microbiota

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

How Do They Do It? – Understanding the Success of Marine Invasive Species

From the depths of the oceans to the shallow estuaries and wetlands of our coasts, organisms of the marine environment are teeming with unique adaptations to cope with a multitude of varying environmental conditions. With millions of years and a vast volume of water to call their home, they have become quite adept at developing specialized and unique techniques for survival and – given increasing human mediated transport – biological invasions. A growing world human population and a global economy drives the transportation of goods across the oceans and with them invasive species via ballast water and attached to ship hulls. In any given 24-hour period, there are about 10,000 species being transported across different biogeographic regions. If any of them manage to take hold and establish a range in an exotic habitat, the implications for local ecosystems can be costly. This review on marine invasions highlights trends among successful non-indigenous species (NIS), from vectors of transport to ecological and physiological plasticity. Apart from summarizing patterns of successful invasions, it discusses the implications of how successfully established NIS impact the local environment, economy and human health. Finally, it looks to the future and discusses what questions need to be addressed and what models can tell us about what the outlook on future marine invasions is