95 research outputs found

    How Much Is Winning a Matter of Luck? A Comparison of 3 Ă— 3 and 5v5 Basketball

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    Background: The comparison of team sports based on luck has a long tradition and remains unsolved. A contrast between the new Olympic format three-on-three (3 × 3) and five-on-five (5v5) forms of basketball has never been analyzed and provides a comparison within the same form of sports. Methods: We developed a new method to calculate performance indicators for each team and invented the Relative Score Difference Index, a new competitive balance indicator that allows the comparison of luck in the two basketball forms for both men and women. We collected game-level data about 3 × 3 and 5v5 from the World Cups held between 2010 and 2019 (N = 666). Luck was defined as the difference between the expected and the actual outcomes of games. Using the basketball World Cup data, we applied the Surprise Index, ran probit regression models, and compared the basketball forms on the goodness-of-fit of the models. Results: As we predicted, there are differential effects of luck between game formats and sex, such that the 3 × 3 form depends more on luck and women’s games are less influenced by luck when compared to men’s games. Conclusion: Coaches may better understand the differences between the two forms and sexes regarding luck if they are aware that the 3 × 3 and men’s competitions are usually more influenced by luck. The findings provide a leverage point for testing new performances and competition balance indicators and will acknowledge the number of games we enjoy watching

    The Less Well-Known Little Brothers: The SLC9B/NHA Sodium Proton Exchanger Subfamily—Structure, Function, Regulation and Potential Drug-Target Approaches

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    The SLC9 gene family encodes Na(+)/H(+) exchangers (NHEs), a group of membrane transport proteins critically involved in the regulation of cytoplasmic and organellar pH, cell volume, as well as systemic acid-base and volume homeostasis. NHEs of the SLC9A subfamily (NHE 1–9) are well-known for their roles in human physiology and disease. Much less is known about the two members of the SLC9B subfamily, NHA1 and NHA2, which share higher similarity to prokaryotic NHEs than the SLC9A paralogs. NHA2 (also known as SLC9B2) is ubiquitously expressed and has recently been shown to participate in renal blood pressure and electrolyte regulation, insulin secretion and systemic glucose homeostasis. In addition, NHA2 has been proposed to contribute to the pathogenesis of polycystic kidney disease, the most common inherited kidney disease in humans. NHA1 (also known as SLC9B1) is mainly expressed in testis and is important for sperm motility and thus male fertility, but has not been associated with human disease thus far. In this review, we present a summary of the structure, function and regulation of expression of the SLC9B subfamily members, focusing primarily on the better-studied SLC9B paralog, NHA2. Furthermore, we will review the potential of the SLC9B subfamily as drug targets

    Treatment of acute rhinitis with a nasal spray containing tramazoline and essential oils: a multicenter, uncontrolled, observational trial

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    BACKGROUND: In this observational trial, data were collected on the effectiveness and tolerability/safety of a nasal spray containing tramazoline and essential oils (trade name Rhinospray((R)) Plus) used for symptomatic treatment of acute rhinitis due to common cold. METHODS: The trial was performed in 300 children, adolescents and adults, who were to be treated with Rhinospray((R)) Plus for up to 4 times per day for up to 10 days. Primary endpoints were the change from baseline to final visit in the mean of three single symptom scores (blocked nose, sneezing, and runny nose) and the mean improvement in two quality-of-life parameters (ability to perform normal daytime activities and quality of sleep). RESULTS: A total of 108 children, 30 adolescents and 162 adults were treated with Rhinospray((R)) Plus. No patient discontinued prematurely. There was a mean reduction of 2.0 +/- 0.6 (standard deviation) in nasal symptom scores from baseline to final visit; 297 of 300 of patients (99.0 %) reported an improvement. The mean value for improvement in quality-of-life parameters was 1.3 +/- 0.5. Improvement in daytime activities was reported by all 300 patients (100.0 %) and in quality of sleep by 292 patients (97.4 %). Effectiveness and tolerability were rated as 'very good' or 'good' by 95.4 % and 97.4 % of patients, respectively; the investigators rated effectiveness and tolerability as 'very good' or 'good' for 97.4 % and 100.0 % of patients, respectively. No adverse events were reported. CONCLUSIONS: Community-based patients reported a relief in acute rhinitis symptoms and improvement in quality of life as a result of treatment with Rhinospray((R)) Plus. Treatment was well-tolerated

    Discovery of novel gating checkpoints in the Orai1 calcium channel by systematic analysis of constitutively active mutants of its paralogs and orthologs.

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    In humans, there are three paralogs of the Orai Ca2+ channel that form the core of the store-operated calcium entry (SOCE) machinery. While the STIM-mediated gating mechanism of Orai channels is still under active investigation, several artificial and natural variants are known to cause constitutive activity of the human Orai1 channel. Surprisingly, little is known about the conservation of the gating checkpoints among the different human Orai paralogs and orthologs in other species. In our work, we show that the mutation corresponding to the activating mutation H134A in transmembrane helix 2 (TM2) of human Orai1 also activates Orai2 and Orai3, likely via a similar mechanism. However, this cross-paralog conservation does not apply to the "ANSGA" nexus mutations in TM4 of human Orai1, which is reported to mimic the STIM1-activated state of the channel. In investigating the mechanistic background of these differences, we identified two positions, H171 and F246 in human Orai1, that are not conserved among paralogs and that seem to be crucial for the channel activation triggered by the "ANSGA" mutations in Orai1. However, mutations of the same residues still allow gating of Orai1 by STIM1, suggesting that the ANSGA mutant of Orai1 may not be a surrogate for the STIM1-activated state of the Orai1 channel. Our results shed new light on these important gating checkpoints and show that the gating mechanism of Orai channels is affected by multiple factors that are not necessarily conserved among orai homologs, such as the TM4-TM3 coupling

    Systematic population-wide ecological analysis of regional variability in disease prevalence

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    The prevalence of diseases often varies substantially from region to region. Besides basic demographic properties, the factors that drive the variability of each prevalence are to a large extent unknown. Here we show how regional prevalence variations in 115 different diseases relate to demographic, socio-economic, environmental factors and migratory background, as well as access to different types of health services such as primary, specialized and hospital healthcare. We have collected regional data for these risk factors at different levels of resolution; from large regions of care (Versorgungsregion) down to a 250 by 250 m square grid. Using multivariate regression analysis, we quantify the explanatory power of each independent variable in relation to the regional variation of the disease prevalence. We find that for certain diseases, such as acute heart conditions, diseases of the inner ear, mental and behavioral disorders due to substance abuse, up to 80% of the variance can be explained with these risk factors. For other diagnostic blocks, such as blood related diseases, injuries and poisoning however, the explanatory power is close to zero. We find that the time needed to travel from the inhabited center to the relevant hospital ward often contributes significantly to the disease risk, in particular for diabetes mellitus. Our results show that variations in disease burden across different regions can for many diseases be related to variations in demographic and socio-economic factors. Furthermore, our results highlight the relative importance of access to health care facilities in the treatment of chronic diseases like diabetes

    The Concise Guide to PHARMACOLOGY 2023/24: Transporters

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    \ua9 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate
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