Four Weeks of Probiotic Supplementation Alters the Metabolic Perturbations Induced by Marathon Running: Insight from Metabolomics

Few data are available that describe how probiotics influence systemic metabolism during endurance exercise. Metabolomic profiling of endurance athletes will elucidate mechanisms by which probiotics may confer benefits to the athlete. In this study, twenty-four runners (20 male, 4 female) were block randomised into two groups using a double-blind matched-pairs design according to their most recent Marathon performance. Runners were assigned to 28-days of supplementation with a multi-strain probiotic (PRO) or a placebo (PLB). Following 28-days of supplementation, runners performed a competitive track Marathon race. Venous blood samples and muscle biopsies (vastus lateralis) were collected on the morning of the race and immediately post-race. Samples were subsequently analysed by untargeted 1H-NMR metabolomics. Principal component analysis (PCA) identified a greater difference in the post-Marathon serum metabolome in the PLB group vs. PRO. Univariate tests identified 17 non-overlapped metabolites in PLB, whereas only seven were identified in PRO. By building a PLS-DA model of two components, we revealed combinations of metabolites able to discriminate between PLB and PRO post-Marathon. PCA of muscle biopsies demonstrated no discernible difference post-Marathon between treatment groups. In conclusion, 28-days of probiotic supplementation alters the metabolic perturbations induced by a Marathon. Such findings may be related to maintaining the integrity of the gut during endurance exercise

Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity.

BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods. RESULTS: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity. CONCLUSION: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens

Bimodal Expansion of the Lymphatic Vessels Is Regulated by the Sequential Expression of IL-7 and Lymphotoxin α1β2 in Newly Formed Tertiary Lymphoid Structures.

Lymphangiogenesis associated with tertiary lymphoid structure (TLS) has been reported in numerous studies. However, the kinetics and dynamic changes occurring to the lymphatic vascular network during TLS development have not been studied. Using a viral-induced, resolving model of TLS formation in the salivary glands of adult mice we demonstrate that the expansion of the lymphatic vascular network is tightly regulated. Lymphatic vessel expansion occurs in two distinct phases. The first wave of expansion is dependent on IL-7. The second phase, responsible for leukocyte exit from the glands, is regulated by lymphotoxin (LT)βR signaling. These findings, while highlighting the tight regulation of the lymphatic response to inflammation, suggest that targeting the LTα1β2/LTβR pathway in TLS-associated pathologies might impair a natural proresolving mechanism for lymphocyte exit from the tissues and account for the failure of therapeutic strategies that target these molecules in diseases such as rheumatoid arthritis

Identification of new transitions and mass assignments of levels in 143−153^{143-153}Pr

The previously reported levels assigned to 151,152,153Pr have recently been called into question regarding their mass assignment. The above questioned level assignments are clarified by measuring g-transitions tagged with A and Z in an in-beam experiment in addition to the measurements from 252Cf spontaneous fission (SF) and establish new spectroscopic information from $N=84$ to $N=94$ in the Pr isotopic chain. The isotopic chain 143-153Pr has been studied from the spontaneous fission of 252Cf by using Gammasphere and also from the measurement of the prompt g-rays in coincidence with isotopically-identified fission fragments using VAMOS++ and EXOGAM at GANIL. The latter were produced using 238U beams on a 9Be target at energies around the Coulomb barrier. The g-g-g-g data from 252Cf (SF) and those from the GANIL in-beam A- and Z-gated spectra were combined to unambiguously assign the various transitions and levels in 151,152,153Pr and other isotopes. New transitions and bands in 145,147,148,149,150Pr were identified by using g-g-g and g-g-g-g coincidences and A and Z gated g-g spectra. The transitions and levels previously assigned to 151,153Pr have been confirmed by the (A,Z) gated spectra. The transitions previously assigned to 152Pr are now assigned to 151Pr on the basis of the (A,Z) gated spectra. Two new bands with 20 new transitions in 152Pr and one new band with 7 new transitions in 153Pr are identified from the g-g-g-g coincidence spectra and the (A,Z) gated spectrum. In addition, new g-rays are also reported in 143-146Pr. New levels of 145,147-153Pr have been established, reliable mass assignments of the levels in 151,152,153Pr have been reported and new transitions have been identified in 143-146Pr showing the new avenues that are opened by combining the two experimental approaches.Comment: Accepted in Phys. Rev.

Parametric Probabilistic Seismic Performance Assessment Framework for Ordinary Standard Bridges

This paper focuses on the assembly and implementation of a full-fledged parametric probabilistic seismic performance assessment framework for ordinary standard bridges (OSBs) in California. The framework stems from the performance-based earthquake engineering (PBEE) assessment methodology developed under the auspices of the Pacific Earthquake Engineering Research (PEER) Center. It involves a sequential execution of analytical steps to arrive at estimates of performance measures which, for example as considered in this study, are the mean return periods (MRPs) of exceedances for a selected set of limit-states (LSs). Improvements from state-of-the-art literature related to various stages of the PEER PBEE assessment framework are incorporated. This includes: (1) introduction of an improved intensity measure (IM), i.e., average spectral acceleration over a period range, for probabilistic seismic hazard analysis (PSHA), (2) conditional mean spectrum (CMS)-based site-specific risk-consistent ground motions selection for ensemble nonlinear time-history analyses involved in probabilistic seismic demand hazard analysis (PSDemHA), (3) introduction of material strain-based engineering demand parameters (EDPs), (4) identification of practical damage LSs, and (5) development of strain-based fragility functions required in probabilistic seismic damage hazard analysis (PSDamHA) for the considered LSs. Four distinct testbed OSBs are selected for the study. A two-dimensional design parameter space is defined in terms of typical primary design variables involved in seismic design of OSBs, i.e., the column diameter and the column longitudinal steel reinforcement ratio. Computational models of the as-designed bridges as well as their re-designs spawned by varying the primary design variables subject to practical constraints are assessed using the implemented framework. For each testbed OSB, and for each of the considered LSs, a smooth surface is fitted to the MRPs computed for all the re-designs of the bridge in the primary design parameter space. Topologies of these surfaces are explored. Feasible design domains in the two-dimensional design parameter space are identified. Safety of the as-designed version and feasibility domain for the re-designs of each testbed OSB are examined and discussed.Support of this research by the California Department of Transportation under Grant No. 65A0594, Task No. 2880 is gratefully acknowledged. Opinions and findings in this study are those of the authors and do not necessarily reflect the views of the sponsor

Recomendaciones para gestantes con diabetes: conclusiones del Consenso reunido por convocatoria del Comité de Diabetes y Embarazo de la SAD

La diabetes gestacional es una alteración de la tolerancia a la glucosa con severidad variable que comienza o es reconocida por primera vez durante el embarazo en curso. Esta definición es válida independientemente del tratamiento que requiera, de si se trata de una diabetes previa al embarazo que no fue diagnosticada, o si la alteración del metabolismo hidrocabonado persiste al concluir la gestación. El presente trabajo, realizado por Consenso en el Comité de Diabetes y Embarazo de la Sociedad Argentina de Diabetes, actualiza los criterios diagnósticos de la diabetes gestacional, así como también el tratamiento, seguimiento y control de la patología tanto durante la gestación, como en el parto y el puerperio.Fil: Faingold, María Cristina.Fil: Lamela, C..Fil: Gheggi, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lapertosa, Silvia.Fil: Di Marco, Ingrid.Fil: Basualdo, María Natalia.Fil: Rovira, Marta Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Glatstein, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: López, C..Fil: Caamaño, A..Fil: Salcedo, L..Fil: Rodríguez, María Elena.Fil: Alvariñas J.

Specific micronutrient concentrations are associated with inflammatory cytokines in a rural population of Mexican women with a high prevalence of obesity

It has been recognised recently that obese individuals have lower concentrations of micronutrients and this may affect the concentrations of inflammatory cytokines. A cross-sectional study was carried out to evaluate the association of specific micronutrients' status with chronic inflammation caused by obesity in 280 women (36·1 (sd 7·5) years) from seven rural communities in Mexico. Measurements of weight, height and waist circumference were made on all women and body composition was determined by dual-energy X-ray absorptiometry. Concentrations of the cytokines IL-1, TNF-α, IL-6, IL-10 and IL-12, lipid profile, and the micronutrients Zn and vitamins A, C and E were determined in fasting blood samples. Ordered logistic regression models were used to determine associations between categorised cytokine levels and micronutrients. It was found that 80 % of women were overweight or obese, and had significantly higher concentrations of C-reactive protein than normal-weight women (P = 0·05). The risk of higher levels of TNF-α, IL-6, IL-10 and IL-12 was reduced significantly among women with higher Zn concentrations (OR 0·63, 95 % CI 0·42, 0·96, P = 0·03; OR 0·57, 95 % CI 0·39, 0·86, P = 0·025; OR 0·63, 95 % CI 0·41, 0·96, P = 0·04; OR 0·62, 95 % CI 0·41, 0·95, P = 0·03, respectively). Higher concentrations of vitamin A were slightly associated with reduced risks of higher levels of IL-1 and IL-12 (OR 0·97, 95 % CI 0·95, 0·99, P = 0·03; OR 0·97, 95 % CI 0·94, 0·99, P = 0·03, respectively); when adjusting for BMI, this association was lost. No associations were found between vitamin C or vitamin E:lipids concentrations and inflammatory cytokines. In conclusion, higher Zn concentrations are associated with reduced risks of higher concentration of inflammation markers in a population of women with a high prevalence of obesity

Measurement of 73 Ge(n,γ) cross sections and implications for stellar nucleosynthesis

© 2019 The Author(s). Published by Elsevier B.V.73 Ge(n,γ) cross sections were measured at the neutron time-of-flight facility n_TOF at CERN up to neutron energies of 300 keV, providing for the first time experimental data above 8 keV. Results indicate that the stellar cross section at kT=30 keV is 1.5 to 1.7 times higher than most theoretical predictions. The new cross sections result in a substantial decrease of 73 Ge produced in stars, which would explain the low isotopic abundance of 73 Ge in the solar system.Peer reviewe

Time-of-flight and activation experiments on 147Pm and 171Tm for astrophysics

The neutron capture cross section of several key unstable isotopes acting as branching points in the s-process are crucial for stellar nucleosynthesis studies, but they are very challenging to measure due to the difficult production of sufficient sample material, the high activity of the resulting samples, and the actual (n,γ) measurement, for which high neutron fluxes and effective background rejection capabilities are required. As part of a new program to measure some of these important branching points, radioactive targets of 147Pm and 171Tm have been produced by irradiation of stable isotopes at the ILL high flux reactor. Neutron capture on 146Nd and 170Er at the reactor was followed by beta decay and the resulting matrix was purified via radiochemical separation at PSI. The radioactive targets have been used for time-of-flight measurements at the CERN n-TOF facility using the 19 and 185 m beam lines during 2014 and 2015. The capture cascades were detected using a set of four C6D6 scintillators, allowing to observe the associated neutron capture resonances. The results presented in this work are the first ever determination of the resonance capture cross section of 147Pm and 171Tm. Activation experiments on the same 147Pm and 171Tm targets with a high-intensity 30 keV quasi-Maxwellian flux of neutrons will be performed using the SARAF accelerator and the Liquid-Lithium Target (LiLiT) in order to extract the corresponding Maxwellian Average Cross Section (MACS). The status of these experiments and preliminary results will be presented and discussed as well