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In this study, allele and genotype frequencies of the ADRB1 Arg389Gly (rs1801253), ADRB2 Gly16Arg (rs1042713) and Gln27Glu (rs1042714), and ADRB3 Trp64Arg (rs4994) variations were compared in the following three groups of Spanish (Caucasian) men: (1) world-class endurance athletes (E; runners and cyclists, n=100), (2) elite power athletes (P; sprinters, jumpers and throwers, n=53) and (3) non-athletic controls (C; n=100). No significant differences were observed in genotype and allele distributions among the study groups except for the ADRB3 Trp64Arg polymorphism in E versus C (27% vs 8% of carriers of the Arg allele in E and C, p<0.001; frequency of the minor Arg (C) allele of 14% vs 4% in E and C, p=0.001). Heterozygosity for the ADRB3 Trp64Arg polymorphism seems to be associated with elite endurance performance, while other variants of the [beta]-adrenergic receptors' genes do not seem to significantly influence top-level sports performance, at least in athletes of Spanish origin. [ABSTRACT FROM AUTHOR]

Background/objectives: The relationship between macronutrient intake and cognitive decline in older adults with type 2 diabetes mellitus (T2DM) remains underexplored., Methods: This cross-sectional study aimed to evaluate the association between the protein-to-carbohydrate energy ratio (%E:P) and cognitive impairment among 192 elderly T2DM patients. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Self-Administered Gerocognitive Exam (SAGE), while dietary intake data, including (%E:P), was gathered using a validated semi-quantitative food frequency questionnaire., Results: Participants had a mean age of 71 ± 6 years, 46.4% were female, and the median BMI was 30 ± 4 kg/m 2 . After adjusting for confounding variables, patients in the highest (%E:P) tertile showed significantly higher MoCA and SAGE scores compared to those in the lowest tertile ( p < 0.005). We identified an optimal (%E:P) threshold of 0.375 for predicting cognitive impairment, with a sensitivity of 53% and specificity of 64%., Conclusions: These findings suggest that a lower (%E:P) ratio may be a risk factor for cognitive impairment in elderly T2DM patients. Monitoring this ratio may serve as an early detection tool for cognitive deterioration. Moreover, current protein intake recommendations for older adults with T2DM may be insufficient to prevent cognitive impairment. Further research is needed to establish optimal dietary guidelines for this population., Competing Interests: The authors declare no conflicts of interest.

The effect of liver fibrosis on mild cognitive impairment (MCI) and dementia risk in type 2 diabetes mellitus (T2DM) patients is unclear. Therefore, we performed a prospective cross-sectional study on 219 patients with T2DM and older than 60 years to evaluate the association between liver fibrosis, liver steatosis, and cognitive impairment. The Montreal Cognitive Assessment (MoCA) was used to screen for MCI or dementia. Liver fibrosis was estimated using the non-invasive Fibrosis-4 (FIB-4) score, and liver steatosis was assessed with the hepatic steatosis index. The mean age was 71 ± 6 years, 47% were women and according to MoCA cut-off values, 53.88% had MCI and 16.43% had dementia. A moderate or high risk of advanced fibrosis was significantly higher in patients with MCI or dementia compared to those with normal cognition ( p < 0.001). After adjusting for confounders, a FIB-4 score greater than 1.54 was associated with MCI or dementia ( p = 0.039). Multivariate analysis identified age over 70.5 years, antiplatelet medication use, and a FIB-4 score above 1.54 as the most relevant risk factors. Liver fibrosis, but not liver steatosis, is associated with MCI or dementia in older T2DM patients, suggesting that FIB-4 score might be a simple biomarker for the detection of cognitive impairment.

Stratifying patients according to disease severity has been a major hurdle during the COVID-19 pandemic. This usually requires evaluating the levels of several biomarkers, which may be cumbersome when rapid decisions are required. In this manuscript we show that a single nanoparticle aggregation test can be used to distinguish patients that require intensive care from those that have already been discharged from the intensive care unit (ICU). It consists of diluting a platelet-free plasma sample and then adding gold nanoparticles. The nanoparticles aggregate to a larger extent when the samples are obtained from a patient in the ICU. This changes the color of the colloidal suspension, which can be evaluated by measuring the pixel intensity of a photograph. Although the exact factor or combination of factors behind the different aggregation behavior is unknown, control experiments demonstrate that the presence of proteins in the samples is crucial for the test to work. Principal component analysis demonstrates that the test result is highly correlated to biomarkers of prognosis and inflammation that are commonly used to evaluate the severity of COVID-19 patients. The results shown here pave the way to develop nanoparticle aggregation assays that classify COVID-19 patients according to disease severity, which could be useful to de-escalate care safely and make a better use of hospital resources., Competing Interests: There are no conflicts of interest., (© 2022 Elsevier B.V. All rights reserved.)

We investigated the association of the angiotensin converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism, alone or in combination with the α-actinin-3 gene (ACTN3) R577X polymorphism, with jumping (vertical squat and counter-movement jump tests) and sprint ability (30 m dash) in non-athletic, healthy young adults [N = 281 (214 male), mean (SD) age 21 (2) years]. We did not observe any effect of the ACE I/D polymorphism on study phenotypes. We repeated the analyses separately in men and women and the results did not materially change. Likewise, the mean estimates of the study phenotypes were similar in subjects with the genotype combinations ACE II + ID and ACTN3 XX or ACE DD and ACTN3 RR + RX. We found no association between the ACE DD and ACTN3 RR + RX genotype combination and performance (≥90th of the sex-specific percentile). In summary, though the ACE I/D polymorphism is a strong candidate to modulate some exercise-related phenotypes or athletic performance status, this polymorphism, alone or in combination with the ACTN3 R577X polymorphism, does not seem to exert a major influence in the muscle 'explosive' power of young healthy adults, as assessed during multi-joint exercise tests.

In this study, genotype frequencies of several polymorphisms that are candidates to influence sports performance (ie, ACTN3 R577X, ACE ID, PPARGC1A Gly482Ser, AMPD1 C34T, CKMM 985bp/1170bp and GDF8 (myostatin) K153R) were compared in 123 nonathletic controls, 50 professional cyclists, 52 Olympic-class runners and 39 world-class rowers (medallists in world championships, lightweight category). Significant differences in genotype distributions among the groups were not found except for the ACE gene, that is, lower (p<0.05) proportion of II in rowers (10.3%) than in the total subject population (22.3%). In summary, sports performance is likely polygenic with the combined effect of hundreds of genetic variants, one possibly being the ACE ID polymorphism (at least in the sports studied here), but many others remain to be identified.

We studied the A55T, E164K, I225T, K153R and P198A variants in the myostatin (GDF8) gene, muscle strength and mass, and physical function during daily living in 41 nonagenarians [33 women, age range, 90, 97]. No participant carried a mutant allele of the aforementioned variants, except three participants (all women), who carried the R allele of the K153R polymorphism, with one of them (woman aged 96 years) being homozygous. Overall, in KR women muscle phenotype values (1RM leg press and estimated muscle mass) were low-to-normal compared to the whole group (approximately 25th-50th percentile), and their functional capacity (Barthel and Tinetti tests) was normal. In the woman bearing the RR genotype, values of muscle mass and functional capacity were below the 25th percentile. She is the first RR Caucasian whose phenotype has been characterised specifically. In summary, heterozygosity for the GDF8 K153R polymorphism does not seem to exert a negative influence on the muscle phenotypes of women who are at the end of the human lifespan, yet homozygosity might do so. More research on larger cohorts of nonagenarians is needed to corroborate the present findings.

We compared a polygenic profile that combined 33 disease risk-related mutations and polymorphisms among nonathletic healthy control subjects and elite endurance athletes. The study sample comprised 100 healthy Spanish male nonathletic (sedentary) control subjects and 100 male elite endurance athletes. We analyzed 33 disease risk-related mutations and polymorphisms. We computed a health-related total genotype score (TGS, 0-100) from the accumulated combination of the 33 variants. We did not observe significant differences in genotype or allele distributions among groups, except for the rs4994 polymorphism (P < 0.001). The computed health-related TGS was similar among groups (23.8 +/- 1.0 vs. 24.2 +/- 0.8 in control subjects and athletes, respectively; P = 0.553). Similar results were obtained when computing specific TGSs for each main disease category (cardiovascular disease and cancer). We observed no evidence that male elite endurance athletes are genetically predisposed to have lower disease risk than matched nonathletic control subjects.

Whether the Met235Thr (rs699) variation in the angiotensinogen (AGT) gene, encoding a threonine instead of a methionine in codon 235 of the mature protein, is associated with athletic performance remains to be elucidated. We compared the genotype and allele frequencies for the AGT Met235Thr variation (rs699) in 119 nonathletic controls, 100 world-class endurance athletes (professional cyclists, Olympic-class runners), and 63 power athletes (top-level jumpers, throwers, sprinters). Participants were all males and from the same descent (Caucasian) for > or =3 generations. The proportion of the CC genotype was significantly higher in the power group (34.9%) than in either the control (16%) or the endurance group (16%) (p = 0.008 and p = 0.005, respectively). The odds ratio (95% CI) of being a power athlete if the subject has a CC genotype was 1.681 (1.176-2.401), compared with the control group. In summary, the C allele of the AGT Met235Thr polymorphism might favour power sports performance. Although more research is needed, this could be attributed to the higher activity of angiotensin II, a skeletal muscle growth factor.

We analysed seven genetic polymorphisms that are candidates to explain individual variations in human endurance phenotypic traits, at least in Caucasian people (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170 bp/985 + 185 bp, HFE His63Asp, GDF-8 Lys153Arg and PPARGC1A Gly482Ser) in 46 world-class endurance athletes and 123 controls (all Spanish Caucasians). Using the model developed by Williams & Folland we determined (1) the 'total genotype score' (TGS, from the accumulated combination of the seven polymorphisms, with a maximum value of '100' for the theoretically optimal polygenic score) in the non-athlete (control) group, in the athlete group and in the total Spanish population, and (2) the probability for the occurrence of Spanish individuals with the 'perfect' polygenic endurance profile (i.e. TGS = 100). The probability of a Spanish individual possessing a theoretically optimal polygenic profile for up to the seven candidate genetic polymorphisms we studied was very small, i.e. approximately 0.07% (or 1 in 1351 Spanish individuals). The mean TGS was higher in athletes (70.22 +/- 15.58) than in controls (62.43 +/- 11.45) and also higher than predicted for the total Spanish population (60.80 +/- 12.1), suggesting an overall more 'favourable' polygenic profile in the athlete group. However, only three of the best Spanish endurance athletes (who are also amongst the best in the world) had the best possible score for up to six genes and none of them had the optimal profile. Other polymorphisms yet undiscovered as well as several factors independent of genetic endowment may explain why some individuals reach the upper end of the endurance performance continuum.

There is individual variability in the clinical manifestation of McArdle disease, with women generally being more severely affected than men. We compared clinical presentation and exercise capacity between (i) four women with McArdle disease (aged 17, 36, 42 and 70 years) who were also carriers of the K153R variant in the myostatin (GDF-8) gene and in (ii) four women with this disorder matched forage (16, 33, 40 and 69 years), lifestyle, and documented genotype modulators of this disease (ACE, AMPD1 and ACTN3), who did not carry the myostatin variant. Except in the youngest patient, clinical severity was higher in K153R carriers than in their K/K(2) controls (aged 33, 40 and 46 years). Peak cardiorespiratory capacity was very low (< or = 13 mLO(2)/kg/min) in all K153R carriers.

We assessed the possible association between variants of the genes encoding for the angiotensin-converting enzyme ( ACE) and alpha-actinin-3 ( ACTN3) (both individually and combined) and several endurance phenotypic traits, e.g., peak power output (PPO), ventilatory (VT) and respiratory compensation threshold (RCT), among others, in professional road cyclists and sedentary controls (n = 46 each). We applied an ANCOVA test using the aforementioned phenotype traits as dependent variables, ACE and/or ACTN3 genotype as the fixed (independent) factor and age and body mass as covariates. We only found a significant genotype effect with no concomitant covariate effect for ACTN3, with cyclists who were not alpha-actinin-3 deficient (RR + RX genotypes) having higher PPO and VT values than their XX counterparts (mean [SEM]: 7.4 (0.1) vs. 7.1 (0.1) W/kg, p = 0.035; and 4.5 (0.1) vs. 4.3 (0.1) W/kg, p = 0.029, respectively). Cyclists with an "extreme" ACTN3 and ACE genotype combination, i.e., most strength/power oriented (DD + RR/RX), had higher RCT values than those with the "intermediate" combinations (II + RX/RR, p = 0.036; and DD + XX, p = .0004) but similar to those with the most endurance oriented genotype (II + XX). No significant differences (p > 0.05) were found in controls. In summary, in world-class cyclists, we only found an association between ACTN3 genotypes and VT and PPO, and between ACTN3/ACE genotype combinations and RCT.

A 9-year-old boy with McArdle disease, who demonstrated remarkable recovery of objectively measured exercise tolerance after 1 year of follow-up, during which he pursued age-appropriate physical activities. The patient presented 1 year previously with severe myalgia, muscle weakness, proteinuria, hematuria, hyperthermia, and elevated creatine kinase levels after noncompetitive swimming. At that time, he reported a 3-year history of general myalgia and poor exercise tolerance. He was diagnosed with McArdle disease by both biochemical and genetic methods. Subsequently he performed a maximal exercise test and was prescribed a return to age-appropriate physical activity (protected by a pre-exercise dietary consumption of approximately 20 g carbohydrate). At 1-year follow up, he reported no subsequent acute clinical episodes, no general problems with exercise either at school or in ordinary activities, a virtual normalization of serum creatine kinase levels, and a 14% increase in body mass-adjusted peak oxygen uptake (from 18.8 to 21.8 mL O2/kg/min). The results suggest that, with protection by increasing pre-exercise blood glucose with carbohydrate ingestion, a substantially normal lifestyle may be possible in some children with McArdle disease.

McArdle disease is caused by inherited deficit of human muscle glycogen phosphorylase with subsequent blockade in muscle glycogenolysis. Patients usually experience severe exercise intolerance and 'chronic' skeletal muscle damage. We determined circulating levels of 27 cytokines in a group of 31 adult McArdle patients (15 male 16 female; mean (+/-S.E.M.) age: 39+/-3 years) and 29 healthy sedentary controls (14 male, 15 female) before and after an acute exercise bout involving no muscle damage (cycling). Patients had an ongoing state of muscle breakdown even when following a sedentary lifestyle (serum creatine kinase activity at baseline of 2590+/-461 Ul(-1) vs. 97+/-5 Ul(-1) in controls). Under resting conditions, neutrophil count (+20%) and circulating levels of several cytokines were significantly higher (P