Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis

Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions.National Funds through Foundation for Science and Technology (FCT) Norte-01-0145-FEDER-000012 Portuguese Foundation for Science and Technology (FCT) SFRH/BD/77056/2011 European Regional Development Fund (FEDER) Norte-01-0145-FEDER-000012info:eu-repo/semantics/publishedVersio

Prevalence of Forced Sex and Associated Factors among Women and Men in Kisumu, Kenya

Sexual violence is a well-recognized global health problem, albeit with limited population-based data available from sub-Saharan Africa. We sought to measure the prevalence of forced sex in Kisumu, Kenya, and identify its associated factors. The data were drawn from a population-based cross-sectional survey. A two-stage sampling design was used: 40 clusters within Kisumu municipality were enumerated and households within each cluster selected by systematic random sampling. Demographic and sexual histories, including questions on forced sex, were collected privately using a structured questionnaire. The prevalence of forced sex was 13% (women) and 4.5% (men). After adjusting for age and cluster, forced sex among women was associated with transactional sex (OR 2.33; 95%CI 1.38-3.95), having more than two lifetime partners (OR 1.9; 95%CI 1.20-3.30), having postprimary education (OR 1.49; 95%CI 1.04-2.14) and a high economic status (OR 1.87; 95%CI 1.2-2.9). No factors were significantly associated with forced sex among the male respondents. Intimate partners were the most common perpetrators of forced sex among both women (50%) and men (62.1%). Forced sex prevention programs need to target the identified associated factors, and educate the public on the high rate of forced sex perpetrated by intimate partners

Impact of the "when the fun stops, stop" gambling message on online gambling behaviour: a randomised, online experimental study

Background: Safer gambling messages are a common freedom-preserving method of protecting individuals from gambling-related harm. Yet, there is little independent and rigorous evidence assessing the effectiveness of safer gambling messages. In our study, we aimed to test the effect of the historically most commonly-used UK safer gambling message on concurrent gambling behaviour of people who gamble in the UK. / Methods: In this study, three preregistered, incentivised, and randomised online experiments, testing the UK's “when the fun stops, stop” message, were carried out via the crowdsourcing platform Prolific. Adults based in the UK who had previously participated in the gambling activities relevant to each experiment were eligible to participate. Experiments 1 and 3 involved bets on real soccer events, and experiment 2 used a commercially available online roulette game. Safer gambling message presence was varied between participants in each experiment. In experiment 2, exposed participants could be shown either a yellow or a black-and-white version of the safer gambling message. Participants were provided with a monetary endowment with which they were allowed to bet. Any of this money not bet was afterwards paid to participants as a bonus, in addition to the payouts from any winning bets. In experiment 2 participants had the opportunity to re-wager any winnings from the roulette game. The primary outcome in experiment 1 was participants’ decisions to accept (or reject) a series of football bets, which varied in their specificity (and payoffs), and the primary outcomes of experiments 2 and 3 were the proportion of available funds bet, which were defined as the total amount of money bet by a participant out of the total that could have been bet. / Findings: Participants for all three experiments were recruited between May 17, 2019, and Oct 17, 2020. Of the 506 participants in experiment 1, 41·3% of available bets were made by the 254 participants in the gambling message condition, which was not significantly different (p=0·15, odds ratio 1·22 [95% CI 0·93 to 1·61]) to the 37·8% of available bets made by the 252 participants in the control condition. In experiment 2, the only credible difference between conditions was that the 501 participants in the condition with the yellow version of the gambling message bet 3·64% (95% Bayesian credibility interval 0·00% to 7·27%) more of available funds left over than the 499 participants in the control condition. There were no credible differences between the bets made by the 500 participants in the black-and-white gambling message condition and the other conditions. In experiment 3, there were no credible differences between the 502 participants in the gambling message condition and the 501 participants in the control condition, with the largest effect being a 5·87% (95% Bayesian credibility interval –1·44% to 13·20%) increase in the probability of betting everything in the gambling message condition. / Interpretation: In our study, no evidence was found for a protective effect of the most common UK safer gambling message. Alternative interventions should be considered as part of an evidence-based public health approach to reducing gambling-related harm. / Funding: University of Warwick, British Academy and Leverhume, Swiss National Science Foundation

Rotation of electromagnetic fields and the nature of optical angular momentum

The association of spin and orbital angular momenta of light with its polarization and helical phase fronts is now well established. The problems in linking this with electromagnetic theory, as expressed in Maxwell's equations, are rather less well known. We present a simple analysis of the problems involved in defining spin and orbital angular momenta for electromagnetic fields and discuss some of the remaining challenges. Crucial to our investigation is the duplex symmetry between the electric and magnetic fields

Which activities threaten independent living of elderly when becoming problematic : inspiration for meaningful service robot functionality

Purpose: In light of the increasing elderly population and the growing demand for home care, the potential of robot support is given increasing attention. In this paper, an inventory of activities was made that threaten independent living of elderly when becoming problematic. Results will guide the further development of an existing service robot, the Care-O-bot®. Method: A systematic literature search of PubMed was performed, focused on the risk factors for institutionalization. Additionally, focus group sessions were conducted in the Netherlands, United Kingdom and France. In these focus group sessions, problematic activities threatening the independence of elderly people were discussed. Three separate target groups were included in the focus group sessions: (1) elderly persons (n = 41), (2) formal caregivers (n = 40) and (3) informal caregivers (n = 32). Results: Activities within the International Classification of Functioning domains mobility, self-care, and interpersonal interaction and relationships were found to be the most problematic. Conclusions: A distinct set of daily activities was identified that may threaten independent living, but no single activity could be selected as the main activity causing a loss of independence as it is often a combination of problematic activities that is person-specific. Supporting the problematic activities need not involve a robotic solution Read More: http://informahealthcare.com/doi/abs/10.3109/17483107.2013.840861Peer reviewe

An unexpected twist to the activation of IKKβ:TAK1 primes IKKβ for activation by autophosphorylation

IKKβ {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase β} is required to activate the transcription factor NF-κB, but how IKKβ itself is activated in vivo is still unclear. It was found to require phosphorylation by one or more ‘upstream’ protein kinases in some reports, but by autophosphorylation in others. In the present study, we resolve this contro-versy by demonstrating that the activation of IKKβ induced by IL-1 (interleukin-1) or TNF (tumour necrosis factor) in embryonic fibroblasts, or by ligands that activate Toll-like receptors in macrophages, requires two distinct phosphorylation events: first, the TAK1 [TGFβ (transforming growth factor β)-activated kinase-1]-catalysed phosphorylation of Ser(177) and, secondly, the IKKβ-catalysed autophosphorylation of Ser(181). The phosphorylation of Ser(177) by TAK1 is a priming event required for the subsequent autophosphorylation of Ser(181), which enables IKKβ to phosphorylate exogenous substrates. We also provide genetic evidence which indicates that the IL-1-stimulated, LUBAC (linear ubiquitin chain assembly complex)-catalysed formation of linear ubiquitin chains and their interaction with the NEMO (NF-κB essential modulator) component of the canonical IKK complex permits the TAK1-catalysed priming phosphorylation of IKKβ at Ser(177) and IKKα at Ser(176). These findings may be of general significance for the activation of other protein kinases

The dynamics of temperature extremes

Changes in the occurrence of atmospheric circulation patterns are not well understood. A study finds that these have been a big factor in observed changes in regional temperature extremes during recent decades

Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF-TIMI 48 Trial.

BACKGROUND: The impact of different types of extracranial bleeding events on health-related quality of life and health-state utility among patients with atrial fibrillation is not well understood. METHODS AND RESULTS: The ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol-5D (EQ-5D-3L) questionnaire, prospectively collected at 3-month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health-state utility over 12 months following the event. Longitudinal mixed-effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (-0.029 [-0.044 to -0.014; P<0.001] and -0.029 [-0.046 to -0.012; P=0.001], respectively). These effects decreased in magnitude over time, and were no longer significant for major nongastrointestinal bleeds at 9 months, but remained borderline significant for major gastrointestinal bleeds at 12 months. Clinically relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility (-0.010 [-0.016 to -0.005] and -0.016 [-0.024 to -0.008]; P<0.001 for both), which remained relatively constant and statistically significant over the 12 months following the bleeding event. CONCLUSIONS: All categories of bleeding events were associated with negative impacts on health-state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391

Socio-Economic Instability and the Scaling of Energy Use with Population Size

The size of the human population is relevant to the development of a sustainable world, yet the forces setting growth or declines in the human population are poorly understood. Generally, population growth rates depend on whether new individuals compete for the same energy (leading to Malthusian or density-dependent growth) or help to generate new energy (leading to exponential and super-exponential growth). It has been hypothesized that exponential and super-exponential growth in humans has resulted from carrying capacity, which is in part determined by energy availability, keeping pace with or exceeding the rate of population growth. We evaluated the relationship between energy use and population size for countries with long records of both and the world as a whole to assess whether energy yields are consistent with the idea of an increasing carrying capacity. We find that on average energy use has indeed kept pace with population size over long time periods. We also show, however, that the energy-population scaling exponent plummets during, and its temporal variability increases preceding, periods of social, political, technological, and environmental change. We suggest that efforts to increase the reliability of future energy yields may be essential for stabilizing both population growth and the global socio-economic system