Meta-analysis of association between ALDH2 rs671 polymorphism and essential hypertension in Asian populations

Background: Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is an enzyme that oxidizes acetaldehyde into acetic acid during alcohol metabolism. Many studies indicate that the rs671 GG genotype in the ALDH2 gene may play a critical role in increasing the risk of essential hypertension (EH) associated with alcohol consumption, which predominantly occurs in men. However, the literature is inconclusive in this regard. This meta-analysis aims to derive a more precise estimation of the relationship between the rs671 polymorphism and EH for both male and female drinkers and nondrinkers. Methods: Ten cohort and case-control studies were included in the analysis with a total of 12,161 subjects; 7,062 patients and 5,099 healthy controls. Results: Our results show that the rs671 GG genotype was associated with an increased risk of EH compared with the AG+AA genotype (OR = 1.27, 95 % CI = 1.17–1.37, p \u3c 0.00001). When comparing male and female subjects, only among male individuals was a higher risk of EH found in the GG genotype compared with the AG+ AA genotype (OR = 1.59, 95 % CI = 1.40–1.80, p \u3c 0.00001). By contrast, among female subjects, the risk of EH in the rs671 GG genotype did not differ from that detected in the AA + GG genotype. The proportion of patients with EH was significantly higher for the GG genotype carriers than for the AG+AA genotype carriers, both in the subset of drinkers (OR = 1.51, 95 % CI = 1.23–1.86, p \u3c 0.0001) and in that of nondrinkers (OR = 1.22, 95 % CI = 1.01–1.47, p = 0.03). In addition, among carriers of the GG genotype, the risk of EH among the drinkers was similar to that found in the nondrinkers’ subset (OR = 1.12, 95 %CI = 0.89–1.41, p = 0.34). Conclusions: Our meta-analysis demonstrates that the rs671 GG genotype increases the risks of EH, especially in men, and is independent of alcohol consumption

Full paper: Airflow dynamics of coughing and sneezing in healthy human volunteers from shadowgraph imaging: An aid to aerosol infection control

10th International Conference on Healthy Buildings 201221302-130

Controlled coupling of an ultrapotent auristatin warhead to cetuximab yields a next-generation antibody-drug conjugate for EGFR-targeted therapy of KRAS mutant pancreatic cancer

Background: Antibody-drug conjugate (ADC) construction poses numerous challenges that limit clinical progress. In particular, common bioconjugation methods afford minimal control over the site of drug coupling to antibodies. Here, such difficulties are overcome through re-bridging of the inter-chain disulfides of cetuximab (CTX) with auristatin-bearing pyridazinediones, to yield a highly refined anti-epidermal growth factor receptor (EGFR) ADC. / Methods: In vitro and in vivo assessment of ADC activity was performed in KRAS mutant pancreatic cancer (PaCa) models with known resistance to CTX therapy. Computational modelling was employed for quantitative prediction of tumour response to various ADC dosing regimens. / Results: Site-selective coupling of an auristatin to CTX yielded an ADC with an average drug:antibody ratio (DAR) of 3.9, which elicited concentration- and EGFR-dependent cytotoxicity at sub-nanomolar potency in vitro. In human xenografts, the ADC inhibited tumour growth and prolonged survival, with no overt signs of toxicity. Key insights into factors governing ADC efficacy were obtained through a robust mathematical framework, including target-mediated dispositional effects relating to antigen density on tumour cells. / Conclusions: Together, our findings offer renewed hope for CTX in PaCa therapy, demonstrating that it may be reformatted as a next-generation ADC and combined with a predictive modelling tool to guide successful translation

Worldwide inequality in access to full text scientific articles: the example of ophthalmology

Ophthalmic researc