Effect of Iron Supplementation on the Modulation of Iron Metabolism, Muscle Damage Biomarkers and Cortisol in Professional Cyclists

Background: The intense efforts made during 3-week stage races may reduce iron metabolism and hematological parameters. These efforts may increase the levels of circulating muscle damage markers and some hormones. All of these physiological changes may have negative consequences not only for the performance of athletes but also for their health. The main aim of this study was to evaluate the effects of supplementation with 80 mg/day of iron on haematological parameters, serum cortisol and biochemical muscle indicators on elite male cyclists during the 3-week stage race the Vuelta a España. Our secondary aim was to examine whether the hematological profile is associated with muscular damage parameters and cortisol. Methods: Eighteen elite male cyclists from two teams were randomly assigned to one of two groups: (1) control group (CG, n = 9; age: 26.1 ± 4.6 years; maximum oxygen uptake per kg: 78.0 ± 5.4 mL/kg/min) or (2) group treated with 80 mg/day iron (800 mg of iron protein succinylate, ITG, n = 9; age: 25.7 ± 6.4 years; maximum oxygen uptake per kg: 77.6 ± 6.5 mL/kg/min). The cyclists were subjected to blood tests one week before the start of the race (T1) and after 4 weeks of treatment, coinciding with the end of the competition (T2). Iron metabolism parameters, muscle damage indicators and serum cortisol were assessed. Repeated-measures ANOVA with group as a factor (GC and ITG) were used to examine the differences between groups throughout the study (time × group) after iron supplementation treatment. Results: Significant differences were observed between groups throughout the study in the group-by-time interaction and changes in serum iron (GC: -8.93 ± 10.35% vs. ITG: 0.60 ± 8.64%; p = 0.018), ferritin (GC: -13.88 ± 23.53% vs. ITG: 91.08 ± 118.30%; p = 0.004), haemoglobin (GC: 10.00 ± 3.32% vs. ITG: 13.04 ± 5.64%; p < 0.001), haematocrit (GC: -1.17 ± 3.78% vs. ITG: 7.32 ± 3.92%; p < 0.001) and cortisol (GC: 24.74 ± 25.84% vs. ITG: ⁻13.54 ± 13.61%; p = 0.005). However, no significant group-by-time interaction was observed for the circulating muscle biomarkers. Additionally, significant negative correlations of serum iron, haemoglobin and haematocrit with muscle circulating biomarkers and cortisol (p < 0.05) were observed. Conclusions: Oral iron supplementation with 80 mg/day iron (800 mg of iron protein succinylate) effectively prevented a decline in haematological parameters (serum iron, ferritin, haemoglobin and haematocrit) and maintained optimal levels of recovery in elite cyclists during the Vuelta a España. Moreover, the hematological values were shown to have relationship with muscular recovery parameters

Effect of pH on the production of hydrolytic enzymes of industrial interest by Bacillus licheniformis using sewage sludge as a low-cost culture médium

Management of sewage sludge has become a topic of increasing importance. This is because the treatment and final destination of these wastes are not growing at the same rate at which generated what is necessary to add the limited storage capacity of wastewater treatment plants or waste transfer centers. Current policies of different governments aims, among others, promote proecological management of sewage sludge, replacing traditional methods by new methods that lead to their stabilization and safe recycling. These methods can lead to the recovery of valuable raw materials from potentially dangerous others in order to permit their use in agriculture, industry or energy production. Moreover, exists a great enzyme market, mainly those with hydrolytic activities such as proteases, lipases or cellulases. Although its use has many advantages, the competitiveness of the enzymes compared with chemicals is limited by its high production costs. The use of a less expensive culture media and the stimulation of the production of these enzymes can significantly reduce production costs. Therefore, the use of tertiary materials as alternative substrates, available in large quantities and at lower cost, is an interesting option. In this work we have studied the effect of pH on the fermentation of sewage sludge by Bacillus licheniformis, a hydrolytic enzymes producer microorganism, in order to obtain several products for specific agronomic applications

Adherence to treatment and related factors among patients with chronic conditions in primary care: a cross-sectional study

Background: Adherence to treatment, a public health issue, is of particular importance in chronic disease therapies. Primary care practices offer ideal venues for the effective care and management of these conditions. The aim of this study is to assess adherence to treatment and related-factors among patients with chronic conditions in primary care settings. Methods: A cross-sectional study was conducted among 299 adult patients with ≥1 chronic condition(s) and prescribed medication in primary healthcare centers of Spain. The Morisky-Green-Levine questionnaire was used to assess medication adherence via face-to-face interviews. Crude and adjusted multivariable logistic regression models were used to analyze factors associated with adherence using the Multidimensional Model proposed by the World Health Organization — social and economic, healthcare team and system-related, condition-related, therapy-related, and patient-related factors. Results: The proportion of adherent patients to treatment was 55.5%. Older age (adjusted odds ratio 1.31 per 10- year increment, 95% CI 1.01–1.70), lower number of pharmacies used for medication refills (0.65, 95% CI 0.47– 0.90), having received complete treatment information (3.89, 95% CI 2.09–7.21), having adequate knowledge about medication regimen (4.17, 95% CI 2.23–7.80), and self-perception of a good quality of life (2.17, 95% CI 1.18–4.02) were independent factors associated with adherence. Conclusions: Adherence to treatment for chronic conditions remained low in primary care. Optimal achievement of appropriate levels of adherence through tailored multifaceted interventions will require attention to the multidimensional factors found in this study, particularly those related to patients’ education and their information needs

Caspase-8 inhibition represses initial human monocyte activation in septic shock model

In septic patients, the onset of septic shock occurs due to the over-activation of monocytes. We tested the therapeutic potential of directly targeting innate immune cell activation to limit the cytokine storm and downstream phases. We initially investigated whether caspase-8 could be an appropriate target given it has recently been shown to be involved in microglial activation. We found that LPS caused a mild increase in caspase-8 activity and that the caspase-8 inhibitor IETD-fmk partially decreased monocyte activation. Furthermore, caspase-8 inhibition induced necroptotic cell death of activated monocytes. Despite inducing necroptosis, caspase-8 inhibition reduced LPS-induced expression and release of IL-1β and IL-10. Thus, blocking monocyte activation has positive effects on both the pro and anti-inflammatory phases of septic shock. We also found that in primary mouse monocytes, caspase-8 inhibition did not reduce LPS-induced activation or induce necroptosis. On the other hand, broad caspase inhibitors, which have already been shown to improve survival in mouse models of sepsis, achieved both. Thus, given that monocyte activation can be regulated in humans via the inhibition of a single caspase, we propose that the therapeutic use of caspase-8 inhibitors could represent a more selective alternative that blocks both phases of septic shock at the source.Unión Europea, Ministerio de Economía y Competitividad SAF2012-39029Unión Europea, Ministerio de Economía y Competitividad SAF2015-64171REspaña,Junta de Andalucía P10-CTS-649

High dose chemotherapy and autologous stem cell transplantation in patients with peripheral T-cell lymphoma not achieving complete response after induction chemotherapy. The GEL-TAMO experience

Background and objectives: patients with aggressive non-Hodgkin's lymphomas (NHL) who do not obtain a complete response (CR) after induction chemotherapy have a poor prognosis. However, provided they are sensitive to the first regimen of chemotherapy, 25-40% of them with a B-cell phenotype may achieve long-term survival when treated with high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT). The aim of this study was to analyze the efficacy of this therapy in the corresponding patients with peripheral T-cell lymphoma (PTCL). Design and methods: we retrospectively evaluated the efficacy of ASCT in 35 patients with PTCL from the GEL-TAMO registry, who did not achieve a CR to standard induction chemotherapy regimens for aggressive NHL. Thirty-one patients underwent transplantation after achieving a partial response (PR) and 4 patients were non-responders. Results: following HDC/ASCT, 23 (66%) of the patients achieved a CR, 4 (11%) a PR and in 7 (20%) cases the transplant failed. One patient was not evaluated because of early toxic death. With a median follow-up of the survivors of 37.5 months, 18 patients (51%) are alive and 15 patients (43%) are free of disease. Transplant-related mortality rate at 100 days was 11% and at 5 years the probabilities of survival, freedom from progression and disease-free survival for complete responders were 37%, 36% and 55% respectively. Pre-transplant lactate-dehydrogenase level, age-adjusted International Prognostic Index (aa-IPI) and tumor score correlated with survival. Interpretation and conclusions: one third of the patients with PTCL who fail to achieve CR to the first chemotherapeutic regimen can be rescued with HDC/ASCT. Pre-transplant values of IPI and tumor score risk systems for aggressive lymphomas were useful to predict subsequent survival

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid involvement had an inferior freedom from central nervous system relapse (P=0.026) but not survival. The amount of intrathecal chemotherapy was quantitatively associated with survival in diffuse large B-cell lymphoma with (P=0.02) and without (P=0.001) occult spinal fluid involvement. However, progression of systemic disease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial

Transition from fireball to Poynting-flux-dominated outflow in the three-episode GRB 160625B

The ejecta composition is an open question in gamma-ray burst (GRB) physics . Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis , suggesting a hot fireball origin. Others show a featureless non-thermal spectrum known as the Band function , consistent with a synchrotron radiation origin and suggesting that the jet is Poynting-flux dominated at the central engine and probably in the emission region as well . There are also bursts showing a sub-dominant thermal component and a dominant synchrotron component , suggesting a probable hybrid jet composition . Here, we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-ray and optical wavelengths, whose prompt emission consists of three isolated episodes separated by long quiescent intervals, with the durations of each sub-burst being approximately 0.8 s, 35 s and 212 s, respectively. Its high brightness (with isotropic peak luminosity L ≈ 4 × 10 erg s) allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to main burst and to extended emission. The spectral properties of the first two sub-bursts are distinctly different, allowing us to observe the transition from thermal to non-thermal radiation between well-separated emission episodes within a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet.B.-B.Z. thanks Y.-Z. Fan, Y.-Z. Wang, H. Wang, K. D. Alexander and D. Lazzati for helpful discussions. We are grateful to K. Hurley, I. Mitrofanov, A. Sanin, M. Litvak and W. Boynton for the use of Mars Odyssey data in the triangulation. We acknowledge the use of the public data from the Swift and Fermi data archives. B.-B. Z. and A.J. C.-T. acknowledge support from the Spanish Ministry Projects AYA2012-39727-C03-01 and AYA2015-71718-R. Part of this work made use of B.-B.Z.'s personal Interactive Data Language (IDL) code library ZBBIDL and personal Python library ZBBPY. The computation resources used in this work are owned by Scientist Support LLC. B.Z. acknowledges NASA NNX14AF85G and NNX15AK85G for support. Z. G. D. acknowledges the National Natural Science Foundation of China(NSFC) (grant 11573014). Y.-D. H. acknowledges support by China Scholarships Council (grant 201406660015). Mini-MegaTORTORA belongs to Kazan Federal University, and the work is performed according to the Russian Government Program of Competitive Growth of Kazan Federal University. A. P., E.M., P. M. and A.V. are grateful to the Russian Foundation for Basic Research (grant 17-02-01388) for partial support. A. P. and S.B.P. acknowledge joint BRICS (Brazil, Russia, India, China and South Africa) grant RFBR 17-52-80139 and 388-ProFChEAP for partial support. R. I. is grateful to grant RUSTAVELI FR/379/6300/ 14 for partial support. Observations on Mini-MegaTORTORA are supported by the Russian Science Foundation (grant 14-50-00043). A.V.F. and A. M. thank the Russian Science Foundation (grant 14-50-00043). L.M. and A.F.Z. acknowledge support from INTA-CEDEA ESAt personnel hosting the Pi of the Sky facility at the BOOTES-1 station. H. G. and X.-Y.W. acknowledge NSFC (grants 11603003 and 11625312, respectively). Z. G. D., X.-F. W., B.Z., X.-Y. W.,L.S. and F.-W.Z. are also supported by the 973 program (grant 2014CB845800). F.-W.Z. is also supported in part by the NSFC (grants U1331101 and 11163003), the Guangxi Natural Science Foundation (grant 2013GXNSFAA019002) and the project of outstanding young teachers' training in higher education institutions of Guangxi. L.S. acknowledges support by the NSFC (grant 11103083) and the Joint NSFC-ISF Research Program (grant 11361140349). S.O. acknowledges the support of the Leverhulme Trust. S.J. acknowledges support from Korea Basic Science Research Program through NRF-2014R1A6A3A03057484 and NRF-2015R1D1A4A01020961, and I. H. P. through NRF-2015R1A2A1A01006870 and NRF-2015R1A2A1A15055344. R. A., D. F. and D. S. acknowledge support from RSF (grant 17-12-01378). A. K. acknowledges the Science and Education Ministry of Kazakhstan (grant 0075/GF4).Peer reviewe

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00233, CB16/12/00284 and CB16/12/00400), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI16/01661, PI16/00517 and PI18/01946), Gerencia Regional de Salud de CyL (GRS 1346/A/16) and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program EDITOR

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