Four Weeks of IV Iron Supplementation Reduces Perceived Fatigue and Mood Disturbance in Distance Runners

To determine the effect of intravenous iron supplementation on performance, fatigue and overall mood in runners without clinical iron deficiency.Fourteen distance runners with serum ferritin 30-100 µg · L(-1) were randomly assigned to receive three blinded injections of intravenous ferric-carboxymaltose (2 ml, 100 mg, IRON) or normal saline (PLACEBO) over four weeks (weeks 0, 2, 4). Athletes performed a 3,000 m time trial and 10 × 400 m monitored training session on consecutive days at week 0 and again following each injection. Hemoglobin mass (Hbmass) was assessed via carbon monoxide rebreathing at weeks 0 and 6. Fatigue and mood were determined bi-weekly until week 6 via Total Fatigue Score (TFS) and Total Mood Disturbance (TMD) using the Brief Fatigue Inventory and Brunel Mood Scale. Data were analyzed using magnitude-based inferences, based on the unequal variances t-statistic and Cohen's Effect sizes (ES).Serum ferritin increased in IRON only (Week 0: 62.8 ± 21.9, Week 4: 128.1 ± 46.6 µg · L(-1); p = 0.002) and remained elevated two weeks after the final injection (127.0 ± 66.3 µg · L(-1), p = 0.01), without significant changes in Hbmass. Supplementation had a moderate effect on TMD of IRON (ES -0.77) with scores at week 6 lower than PLACEBO (ES -1.58, p = 0.02). Similarly, at week 6, TFS was significantly improved in IRON vs. PLACEBO (ES -1.54, p = 0.05). There were no significant improvements in 3,000 m time in either group (Week 0 vs. Week 4; Iron: 625.6 ± 55.5 s vs. 625.4 ± 52.7 s; PLACEBO: 624.8 ± 47.2 s vs. 639.1 ± 59.7 s); but IRON reduced their average time for the 10 × 400 m training session at week 2 (Week 0: 78.0 ± 6.6 s, Week 2: 77.2 ± 6.3; ES-0.20, p = 0.004).During 6 weeks of training, intravenous iron supplementation improved perceived fatigue and mood of trained athletes with no clinical iron deficiency, without concurrent improvements in oxygen transport capacity or performance

Co-Crystal Structures of PKG Iβ (92–227) with cGMP and cAMP Reveal the Molecular Details of Cyclic-Nucleotide Binding

Cyclic GMP-dependent protein kinases (PKGs) are central mediators of the NO-cGMP signaling pathway and phosphorylate downstream substrates that are crucial for regulating smooth muscle tone, platelet activation, nociception and memory formation. As one of the main receptors for cGMP, PKGs mediate most of the effects of cGMP elevating drugs, such as nitric oxide-releasing agents and phosphodiesterase inhibitors which are used for the treatment of angina pectoris and erectile dysfunction, respectively. configuration, with a conserved threonine residue anchoring both cyclic phosphate and guanine moieties. The structure of CNBD-A in the absence of bound cyclic nucleotide was similar to that of the cyclic nucleotide bound structures. Surprisingly, isothermal titration calorimetry experiments demonstrated that CNBD-A binds both cGMP and cAMP with a relatively high affinity, showing an approximately two-fold preference for cGMP. conformation through its interaction with Thr193 and an unusual cis-peptide forming residues Leu172 and Cys173. Although these studies provide the first structural insights into cyclic nucleotide binding to PKG, our ITC results show only a two-fold preference for cGMP, indicating that other domains are required for the previously reported cyclic nucleotide selectivity

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

installation art - Frenzy Episode | Contact | Raising the Dead

This monograph presents a series of three exhibitions developed collaboratively by Agnieszka Golda and Martin Johnson. It describes a wonderful tracery of not quite recognisable anthropomorphic creatures who inhabit oddly constructed and disjointed spaces. Together Golda and Johnson have utilised crocheted and printed textiles, carved wood and painted aluminium to form strange dwellings, figures and passages. Dr Ruth Fazakerley\u27s research and art practice span Australian contemporary urban public art, painting and sculptural installation. In her essay here she positions Golda and Johnson\u27s work in a wider context. The distinctive aesthetic force of collaborative process is underpinned by Golda\u27s discerning scholarship in opening up \u27sensography\u27, a terrain that explores both art practice and the emotional, affective resonances it engenders.https://ro.uow.edu.au/inart/1000/thumbnail.jp

Cache Coherence and Storage Management in a Persistent Object System

A distributed architecture for the support of programs written in the persistent programming language Napier is described. The architecture consists of a central server containing the stable persistent store and a collection of clients, each executing Napier processes. Since each client has a cache of objects, some of which may be shared with other clients, a protocol is required to ensure that the caches are coherent and that any access of an object will be to the most up-to- date copy. This architecture is explicated by following the lifecycle of an object from its ‘birth’ inside a client, through its life in the persistent store and its migration into other clients. Using this vehicle, the coherency protocol and client/server architecture are illustrated and explained

Intravenous iron supplementation in distance runners with low or suboptimal ferritin

Purpose: Iron deficiency is prevalent in distance runners and may impair endurance performance. The current practice of oral supplementation is slow and often not well tolerated. The aim of this study was to assess the efficacy of intravenous (IV) iron supplementation (ferric carboxymaltose) compared with oral supplementation (ferrous sulfate) on iron status, hemoglobin mass (Hbmass), and physiological indices of running performance in distance runners. Methods: Twenty-seven highly trained distance runners with low (LOW) (ferritin < 35 [mu]g[middle dot]L-1 and transferrin saturation < 20%, or ferritin < 15 [mu]g[middle dot]L-1) or suboptimal (SUB) iron status (ferritin < 65 [mu]g[middle dot]L-1) were supplemented with either IV iron (Ferinject(R)) or oral (ORAL) supplements (Ferrogradumet) for 6 wk. Iron status and Hbmass were assessed before supplementation and at 1, 2, 4, 6, and 8 wk in the four groups (IV LOW, IV SUB, ORAL LOW, and ORAL SUB). In addition, athletes completed a treadmill running test for running economy, lactate threshold, and V[spacing dot above]O2max before and after supplementation. Results: Both forms of supplementation substantially increased ferritin levels in all four groups. IV supplementation resulted in higher ferritin in both IV groups compared with both ORAL groups from week 1 onward. Hemoglobin concentration did not change substantially in any group. Hbmass increased in IV LOW (mean = +4.9%, 90% confidence interval [CI] = 1.1%-8.9%) and was accompanied by an increase in V[spacing dot above]O2max (mean = +3.3%, 90% CI = 0.4%-6.3%) and run time to exhaustion (mean = +9.3%, 90% CI = 0.9%-18.3%. Conclusions: IV supplementation can effectively increase iron stores in iron-deficient runners within 6 wk and, if Hbmass is compromised, may enhance endurance capacity by facilitating erythropoiesis. Hbmass appears a more sensitive tool for measuring changes in whole body hemoglobin than hemoglobin concentration and may be useful in the diagnosis and follow-up for iron deficiency

Iron parameters, Hbmass,[Hb] and fatigue scores of IRON and PLACEBO groups pre-supplementation and at 2, 4 and 6 weeks post-supplementation.

<p>Mean ± SD; * denotes significant difference (p≤0.05) from week 0 values within a group.</p>†<p>significant difference (p≤0.05) between groups at matched time point.</p><p>Hbmass: haemoglobin mass, [Hb]: haemoglobin concentration, Hct: Haematocrit, TSAT: percent transferrin saturation.</p><p>Iron parameters, Hbmass,[Hb] and fatigue scores of IRON and PLACEBO groups pre-supplementation and at 2, 4 and 6 weeks post-supplementation.</p