A sportomics soccer investigation unveils an exercise-induced shift in tyrosine metabolism leading to hawkinsinuria

Tyrosine metabolism has an intense role in the synthesis of neurotransmitters. Our study used an untargeted, sportomics-based analysis of urine samples to investigate changes in metabolism during a soccer match in 30 male junior professional soccer players. Samples were collected before and after the match and analyzed using liquid chromatography and mass spectrometry. Results showed significant changes in tyrosine metabolism. Exercise caused a downregulation of the homogentisate metabolites 4-maleylacetoacetate and succinylacetone to 20% (p = 4.69E−5) and 16% (p = 4.25E−14), respectively. 4-Hydroxyphenylpyruvate, a homogentisate precursor, was found to be upregulated by 26% (p = 7.20E−3). The concentration of hawkinsin and its metabolite 4-hydroxycyclohexyl acetate increased ~six-fold (p = 1.49E−6 and p = 9.81E−6, respectively). Different DOPA metabolism pathways were also affected by exercise. DOPA and dopaquinone increased four-to six-fold (p = 5.62E−14 and p = 4.98E−13, respectively). 3-Methoxytyrosine, indole-5,6-quinone, and melanin were downregulated from 1 to 25%, as were dopamine and tyramine (decreasing to up to 5% or 80%; p= 5.62E−14 and p = 2.47E−2, respectively). Blood TCO2 decreased as well as urinary glutathione and glutamate (40% and 10% respectively) associated with a two-fold increase in pyroglutamate. Our study found unexpected similarities between exercise-induced changes in metabolism and the inherited disorder Hawkinsinuria, suggesting a possible transient condition called exercise-induced hawkinsinuria (EIh). Additionally, our research suggests changes in DOPA pathways may be involved. Our findings suggest that soccer exercise could be used as a model to search for potential countermeasures in Hawkinsinuria and other tyrosine metabolism disorders

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Latitude gradient influences the age of onset of rheumatoid arthritis : a worldwide survey

The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10A degrees increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 +/- 14 years (95% CI 44-45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p <0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R (2) 0.045, p <0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p <0.01, R (2) 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza a(H1N1)pdm09 and B among elderly people in Europe: Results from the I-MOVE+ project

We conducted a multicentre test-negative caseâ\u80\u93control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged â\u89¥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases