Overlap of genetic loci for central serous chorioretinopathy with age-related macular degeneration

IMPORTANCE Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases.OBJECTIVE To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD.DESIGN, SETTING, AND PARTICIPANTS Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in ameta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022.MAIN OUTCOMES AND MEASURES Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by ameta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study.RESULTS A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in ameta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P =.004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P < 7.1 x 10(-20)). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 x 10(-10)). This association may have been mediated by loci containing complement genes.CONCLUSIONS AND RELEVANCE In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.Ophthalmic researc

Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis

Background: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training. However, there is much discrepancy in the literature regarding the proposed benefits of protein supplementation during prolonged resistance-type exercise training in younger and older populations. Objective: The objective of the study was to define the efficacy of protein supplementation to augment the adaptive response of the skeletal muscle to prolonged resistance-type exercise training in younger and older populations. Design: A systematic review of interventional evidence was performed through the use of a random-effects meta-analysis model. Data from the outcome variables fat-free mass (FFM), fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition maximum (1-RM) leg press strength were collected from randomized controlled trials (RCTs) investigating the effect of dietary protein supplementation during prolonged (>6 wk) resistance-type exercise training. Results: Data were included from 22 RCTs that included 680 subjects. Protein supplementation showed a positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91 kg; P <0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg; 95% CI: 6.4, 20.7 kg; P <0.005) compared with a placebo after prolonged resistance-type exercise training in younger and older subjects. Conclusion: Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects

Intragastric protein administration stimulates overnight muscle protein synthesis in elderly men

Groen BB, Res PT, Pennings B, Hertle E, Senden JM, Saris WH, van Loon LJ. Intragastric protein administration stimulates overnight muscle protein synthesis in elderly men. Am J Physiol Endocrinol Metab 302: E52-E60, 2012. First published September 13, 2011; doi:10.1152/ajpendo.00321.2011.-The loss of skeletal muscle mass with aging has been attributed to an impaired muscle protein synthetic response to food intake. Therefore, nutritional strategies are targeted to modulate postprandial muscle protein accretion in the elderly. The purpose of this study was to assess the impact of protein administration during sleep on in vivo protein digestion and absorption kinetics and subsequent muscle protein synthesis rates in elderly men. Sixteen healthy elderly men were randomly assigned to an experiment during which they were administered a single bolus of intrinsically L-[1-(13)C] phenylalanine-labeled casein protein (PRO) or a placebo (PLA) during sleep. Continuous infusions with L-[ring-(2)H(5)] phenylalanine and L-[ring-(2)H(2)] tyrosine were applied to assess in vivo dietary protein digestion and absorption kinetics and subsequent muscle protein synthesis rates during sleep. We found that exogenous phenylalanine appearance rates increased following protein administration. The latter stimulated protein synthesis, resulting in a more positive overnight whole body protein balance (0.30 +/- 0.1 vs. 11.8 +/- 1.0 mu mol phenylalanine.kg(-1).h(-1) in PLA and PRO, respectively; P < 0.05). In agreement, overnight muscle protein fractional synthesis rates were much greater in the PRO experiment (0.045 +/- 0.002 vs. 0.029 +/- 0.002%/h, respectively; P < 0.05) and showed abundant incorporation of the amino acids ingested via the intrinsically labeled protein (0.058 +/- 0.006%/h). This is the first study to show that dietary protein administration during sleep is followed by normal digestion and absorption kinetics, thereby stimulating overnight muscle protein synthesis. Dietary protein administration during sleep stimulates muscle protein synthesis and improves overnight whole body protein balance. These findings may provide a basis for novel interventional strategies to attenuate muscle mass loss

Astaxanthin supplementation does not augment fat use or improve endurance performance.

RES, P. T., N. M. CERMAK, R. STINKENS, T. J. TOLLAKSON, G. R. HAENEN, A. BAST, and L. J. VAN LOON. Astaxanthin Supplementation Does Not Augment Fat Use or Improve Endurance Performance. Med. Sci. Sports Exerc., Vol. 45, No. 6, pp. 1158–1165, 2013. Introduction: Astaxanthin is a lipid-soluble carotenoid found in a variety of aquatic organisms. Prolonged astaxanthin supplementation has been reported to increase fat oxidative capacity and improve running time to exhaustion in mice. These data suggest that astaxanthin may be applied as a potent ergogenic aid in humans. Purpose: To assess the effect of 4 wk of astaxanthin supplementation on substrate use and subsequent time trial performance in well-trained cyclists. Methods: Using a double-blind parallel design, 32 young, well-trained male cyclists or triathletes (age = 25 T 1 yr, weight = 73 T 1 kg, V˙ O2peak = 60 T 1 mLj1 Ikgj1 Iminj1 , Wmax = 395 T 7 W; mean T SEM) were supplemented for 4 wk with 20 mg of astaxanthin per day (ASTA) or a placebo (PLA). Before and after the supplementation period, subjects performed 60 min of exercise (50% Wmax), followed by an time trial of approximately 1 h. Results: Daily astaxanthin supplementation significantly increased basal plasma astaxanthin concentrations from nondetectable values to 187 T 19 KgIkgj1 (P G 0.05). This elevation was not reflected in greater total plasma antioxidant capacity (P = 0.90) or attenuated malondialdehyde levels (P = 0.63). Whole-body fat oxidation rates during submaximal exercise did not differ between groups and did not change over time (from 0.71 T 0.04 to 0.68 T 0.03 gIminj1 and from 0.66 T 0.04 to 0.61 T 0.05 gIminj1 in the PLA and ASTA groups, respectively; P = 0.73). No improvements in time trial performance were observed in either group (from 236 T 9 to 239 T 7 and from 238 T 6 to 244 T 6 W in the PLA and ASTA groups, respectively; P = 0.63). Conclusion: Prolonged astaxanthin supplementation does not augment antioxidant capacity, increase fat oxidative capacity, or improve time trial performance in trained cyclists. Key Words: SUBSTRATE USE, CYCLING, FAT OXIDATION, EXERCISE, ERGOGENIC AIDS, ANTI-OXIDANT

Astaxanthin supplementation does not augment fat use or improve endurance performance.

Rouzé Michel. Les phoques victimes du P.C.B. In: Raison présente, n°83, 3e trimestre 1987. Le besoin de psychiatrie. p. 146

Protein ingestion before sleep improves postexercise overnight recovery.

RES, P. T., B. GROEN, B. PENNINGS, M. BEELEN, G. A. WALLIS, A. P. GIJSEN, J. M. G. SENDEN, and L. J. C. VAN LOON. Protein Ingestion before Sleep Improves Postexercise Overnight Recovery. Med. Sci. Sports Exerc., Vol. 44, No. 8, pp. 1560-1569, 2012. Introduction: The role of nutrition in modulating postexercise overnight recovery remains to be elucidated. We assessed the effect of protein ingestion immediately before sleep on digestion and absorption kinetics and protein metabolism during overnight recovery from a single bout of resistance-type exercise. Methods: Sixteen healthy young males performed a single bout of resistance-type exercise in the evening (2000 h) after a full day of dietary standardization. All subjects were provided with appropriate recovery nutrition (20 g of protein, 60 g of CHO) immediately after exercise (2100 h). Thereafter, 30 min before sleep (2330 h), subjects ingested a beverage with (PRO) or without (PLA) 40 g of specifically produced intrinsically [1-C-13] phenylalanine-labeled casein protein. Continuous intravenous infusions with [ring-H-2(5)] phenylalanine and [ring-H-2(2)] tyrosine were applied with blood and muscle samples collected to assess protein digestion and absorption kinetics, whole-body protein balance and mixed muscle protein synthesis rates throughout the night (7.5 h). Results: During sleep, casein protein was effectively digested and absorbed resulting in a rapid rise in circulating amino acid levels, which were sustained throughout the remainder of the night. Protein ingestion before sleep increased whole-body protein synthesis rates (311 +/- 8 vs 246 +/- 9 mu mol(.)kg(-1) per 7.5 h) and improved net protein balance (61 +/- 5 vs -11 +/- 6 mu mol(.)kg(-1) per 7.5 h) in the PRO vs the PLA experiment (P <0.01). Mixed muscle protein synthesis rates were similar to 22% higher in the PRO vs the PLA experiment, which reached borderline significance (0.059%(.)h(-1) +/- 0.005%(.)h(-1) vs 0.048%(.)h(-1) +/- 0.004%(.)h(-1), P = 0.05). Conclusions: This is the first study to show that protein ingested immediately before sleep is effectively digested and absorbed, thereby stimulating muscle protein synthesis and improving whole-body protein balance during postexercise overnight recovery