Synthesis of N-Glycolylneuraminic Acid (Neu5Gc) and Its Glycosides.

Sialic acids constitute a family of negatively charged structurally diverse monosaccharides that are commonly presented on the termini of glycans in higher animals and some microorganisms. In addition to N-acetylneuraminic acid (Neu5Ac), N-glycolyl neuraminic acid (Neu5Gc) is among the most common sialic acid forms in nature. Nevertheless, unlike most animals, human cells loss the ability to synthesize Neu5Gc although Neu5Gc-containing glycoconjugates have been found on human cancer cells and in various human tissues due to dietary incorporation of Neu5Gc. Some pathogenic bacteria also produce Neu5Ac and the corresponding glycoconjugates but Neu5Gc-producing bacteria have yet to be found. In addition to Neu5Gc, more than 20 Neu5Gc derivatives have been found in non-human vertebrates. To explore the biological roles of Neu5Gc and its naturally occurring derivatives as well as the corresponding glycans and glycoconjugates, various chemical and enzymatic synthetic methods have been developed to obtain a vast array of glycosides containing Neu5Gc and/or its derivatives. Here we provide an overview on various synthetic methods that have been developed. Among these, the application of highly efficient one-pot multienzyme (OPME) sialylation systems in synthesizing compounds containing Neu5Gc and derivatives has been proven as a powerful strategy

Accelerated ageing is associated with increased COVID-19 severity and differences across ethnic groups may exist

BackgroundWhile increased age is an established risk factor for COVID-19, there is great heterogeneity in outcomes within age groups. This is because chronological age does not reflect health, unlike biological age. We intend to investigate the association between accelerated ageing and COVID-19 outcomes through the lens of three measures, namely phenotypic age acceleration (PhenoAgeAccel), telomere length (Adjusted T/S Ratio) and facial ageing, and to examine whether there are differences across ethnic groups.MethodsTaking participants from the UK Biobank, we associated accelerated ageing with severe COVID-19 outcomes, defined as COVID-related hospitalisation or death. Separate logistic regressions models were created for age and the three accelerated ageing-related variables, adjusting for a variety of covariates in each model. Multivariable logistic regression models were also created within White, Black, Asian and Other ethnic groups to assess for potential differing associations. Forward likelihood ratio logistic regression models were created to evaluate importance of the variables and to assess for patterns of association across the total population and ethnic groups.ResultsAfter adjusting for all covariates, the odds ratio (OR) and 95% confidence interval (95% CI) of COVID-19 severe outcomes for age was 1.080 (1.074–1.086). After further adjusting age for the accelerated ageing variables, the ORs were 1.029 (1.020–1.039) for PhenoAgeAccel and 0.847 (0.772–0.929) for Facial Ageing's “Younger Than You Are” while Adjusted T/S ratio and “Older Than You Are” were statistically insignificant. The OR for age remained similar across ethnic groups. Both PhenoAgeAccel and younger facial ages in the White population and PhenoAgeAccel in the Black population had ORs of 1.031 (1.021–1.042), 0.853 (0.774–0.939), and 1.049 (1.001–1.100), respectively. Both Adjusted T/S Ratio and older facial ages showed statistical insignificance in all ethnicities. In forward logistic regression, age and PhenoAgeAccel were the age-related variables selected most frequently in all models.InterpretationAccelerated ageing is associated with increased COVID-19 severity. The mechanisms at work here are likely immunosenescence and inflamaging. This association indicates that anti-ageing treatment may improve COVID-19 outcome. The results within ethnic groups and that of telomere length were inconclusive, but point to a need for future, more focused research on the topic

Evaluation of three accelerometer devices for physical activity measurement amongst south Asians and Europeans

We recruited 62 South Asians and 40 Europeans aged 25 to 75 years, to assess the potential validity of three physical activity accelerometers for use amongst South Asians. Participants completed an exercise treadmill test (following Bruce protocol) while wearing the 3 accelerometers: Actigraph GT3X+ [GT3X+] and Geneactiv [GA] on ankle, waist and wrist; and Actiheart [AH] on chest. We compared relationships between energy expenditure (EE) measured by accelerometers (Measured) and actual EE on the treadmill (Actual) in the two ethnicities and tested for potential confounding effects. All accelerometers under-reported EE. Difference between Measured and Actual EE was smallest for GT3X+ankle (Measured – Actual at peak exercise [Mets]: GT3X+ankle –6.52 (1.77); GT3X+waist –8.46 (1.29); GT3X+wrist –11.17 (1.03); GAankle –8.17 (1.19); GAwaist –10.24 (0.64); GAwrist –11.21 (1.10); AHchest –9.09 (1.43), P 0.05). Relationship between Measured and Actual EE was not influenced by age, gender, height, waist, weight or waist-hip ratio (all P > 0.05). Amongst the devices and positions tested, GT3X+ankle is the most accurate device for measuring EE during an exercise treadmill test. Accelerometer performance is similar in South Asians and Europeans and is not influenced by anthropometric differences between the two populations

Risk factors for progression to blindness in high tension primary open angle glaucoma: Comparison of blind and nonblind subjects

Karanjit S Kooner1, Mohannad AlBdoor1, Byung J Cho3, Beverley Adams-Huet21Department of Ophthalmology, 2Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA; 3Konkuk University Hospital, Seoul, KoreaAims: To determine which risk factors for blindness were most critical in patients diagnosed with high tension primary open angle glaucoma (POAG) in a large ethnically diverse population managed with a uniform treatment strategy.Methods: A longitudinal observational study was designed to follow 487 patients (974 eyes) with POAG for an average of 5.5 ± 3.6 years. Detailed ocular and systemic information was collected on each patient and updated every six months. For this study, blindness was defined as visual acuity of 20/200 or worse and/or visual field less than 20° in either eye. Known risk factors were compared between patients with blindness in at least one eye versus nonblind patients.Results: The patients with blindness had on average: higher intraocular pressure (IOP, mmHg): (24.2 ± 11.2 vs. 22.1 ± 7.7, p = 0.03), wide variation of IOP in the follow-up period (5.9 vs. 4.1 mmHg, p = 0.031), late detection (p = 0.006), poor control of IOP (p < 0.0001), and noncompliance (p < 0.0003). Other known risk factors such as race, age, myopia, family history of glaucoma, history of ocular trauma, hypertension, diabetes, vascular disease, smoking, alcohol abuse, dysthyoidism, and steroid use were not significant.Conclusions: The most critical factors associated with the development of blindness among our patients were: elevated initial IOP, wide variations and poor control of IOP, late detection of glaucoma, and noncompliance with therapy.Keywords: primary open angle glaucoma, blindness, intraocular pressure, risk factors, and noncomplianc