Assessment of practical applicability and clinical relevance of a commonly used LDL-C polygenic score in patients with severe hypercholesterolemia

Background and aims: Low-density lipoprotein cholesterol (LDL-C) levels vary in patients with familial hypercholesterolemia (FH) and can be explained by a single deleterious genetic variant or by the aggregate effect of multiple, common small-effect variants that can be captured in a polygenic score (PS). We set out to investigate the contribution of a previously published PS to the inter-individual LDL-C variation and coronary artery disease (CAD) risk in patients with a clinical FH phenotype. Methods: First, in a cohort of 628 patients referred for genetic FH testing, we evaluated the distribution of a PS for LDL-C comprising 12 genetic variants. Next, we determined its association with coronary artery disease (CAD) risk using UK Biobank data. Results: The mean PS was higher in 533 FH-variant-negative patients (FH/M-) compared with 95 FH-variant carriers (1.02 vs 0.94, p < 0.001). 39% of all patients had a PS equal to the top 20% from a population-based reference cohort and these patients were less likely to carry an FH variant (OR 0.22, 95% CI 0.10–0.48) compared with patients in the lowest 20%. In UK Biobank data, the PS explained 7.4% of variance in LDL-C levels and was associated with incident CAD. Addition of PS to a prediction model using age and sex and LDL-C did not increase the c-statistic for predicting CAD risk. Conclusions: This 12-variant PS was higher in FH/M- patients and associated with incident CAD in UK Biobank data. However, the PS did not improve predictive accuracy when added to the readily available characteristics age, sex and LDL-C, suggesting limited discriminative value for CAD

Modulation in voluntary neural drive in relation to muscle soreness

The aim of this study was to investigate whether (1) spinal modulation would change after non-exhausting eccentric exercise of the plantar flexor muscles that produced muscle soreness and (2) central modulation of the motor command would be linked to the development of muscle soreness. Ten healthy subjects volunteered to perform a single bout of backward downhill walking exercise (duration 30 min, velocity 1 ms−1, negative grade −25%, load 12% of body weight). Neuromuscular test sessions [H-reflex, M-wave, maximal voluntary torque (MVT)] were performed before, immediately after, as well as 1–3 days after the exercise bout. Immediately after exercise there was a −15% decrease in MVT of the plantar flexors partly attributable to an alteration in contractile properties (−23% in electrically evoked mechanical twitch). However, MVT failed to recover before the third day whereas the contractile properties had significantly recovered within the first day. This delayed recovery of MVT was likely related to a decrement in voluntary muscle drive. The decrease in voluntary activation occurred in the absence of any variation in spinal modulation estimated from the H-reflex. Our findings suggest the development of a supraspinal modulation perhaps linked to the presence of muscle soreness

Correction: Genetically predicted neutrophil-to-lymphocyte ratio and coronary artery disease: Evidence from mendelian randomization (Circulation: Genomic and Precision Medicine (2022) 15 (e003553) DOI: 10.1161/CIRCGEN.121.003553)

In the February 2022 issue of Circulation: Genomic and Precision Medicine, the license for the article by Cupido et al (Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization. Circ Genom Precis Med. 2022;15:e003553) has been changed in compliance with funding requirements. The article is published under the creative commons license CC BY. This correction has been made to the article, which is available at: https://www.ahajournals.org/doi/10.1161/ CIRCGEN.121.003553

Current sheets in comet 67P/Churyumov-Gerasimenko's coma

The Rosetta Plasma Consortium (RPC) data are used to investigate the presence of current sheets in the coma of comet 67P/Churyumov-Gerasimenko. The interaction of the interplanetary magnetic field (IMF) transported by the solar wind toward the outgassing comet consists amongst others of mass loading and field line draping near the nucleus. The draped field lines lead to so-called nested draping because of the constantly changing direction of the IMF. It is shown that the draping pattern is strongly variable over the period of one month. Nested draping results in neighbouring regions with oppositely directed magnetic fields, which are separated by current sheets. Selected events on 5 and 6 June 2015 are studied, which show that there are strong rotations of the magnetic field with associated current sheets that have strengths from several tens up to hundreds of nA/m2. Not all discussed current sheets show the characteristic peak in plasma density at the centre of the sheet, which might be related to the presence of a guide field. There is no evidence for different kinds of plasmas on either side of a current sheet, and no strongly accelerated ions have been observed which could have been an indication of magnetic reconnection in the current sheets