Chemical composition of 90 F and G disk dwarfs

High resolution, high S/N spectra have been obtained for a sample of 90 F and G main-sequence disk stars covering the metallicity range -1.0 < [Fe/H] < +0.1, and have been analysed in a parallel way to the work of Edvardsson et al. (1993). Effective temperatures are based on the Alonso et al. (1996) calibration of color indices and surface gravities are calculated from Hipparcos parallaxes, which also allow more accurate ages to be calculated. In addition, more reliable kinematical parameters are derived from Hipparcos distances and proper motions. Finally, a larger spectral coverage, 5600 - 8800 A, makes it possible to improve the abundance accuracy by studying more lines and to discuss several elements not included in the work of Edvardsson et al. The present paper provides the data and discusses some general results of the abundance survey. A group of stars in the metallicity range of -1.0 < [Fe/H] < -0.6 having a small mean Galactocentric distance in the stellar orbits, Rm < 7 kpc, are shown to be older than the other disk stars and probably belong to the thick disk. Excluding these stars, a slight decreasing trend of [Fe/H] with increasing Rm and age is found, but a large scatter in [Fe/H] (up to 0.5 dex) is present at a given age and Rm. The derived trends of O, Mg, Si, Ca, Ti, Ni and Ba as a function of [Fe/H] agree rather well with those of Edvardsson et al., but the overabundance of Na and Al for metal-poor stars found in their work is not confirmed. Furthermore, the Galactic evolution of elements not included in Edvardsson et al., K, V and Cr, is studied.Comment: 16 pages with 10 figures. Accepted for publication in A&A

Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines

Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcome

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition

Urinary secretion and extracellular aggregation of mutant uromodulin isoforms.

Uromodulin is exclusively expressed in the thick ascending limb and is the most abundant protein secreted in urine where it is found in high-molecular-weight polymers. Its biological functions are still elusive, but it is thought to play a protective role against urinary tract infection, calcium oxalate crystal formation, and regulation of water and salt balance in the thick ascending limb. Mutations in uromodulin are responsible for autosomal-dominant kidney diseases characterized by defective urine concentrating ability, hyperuricemia, gout, tubulointerstitial fibrosis, renal cysts, and chronic kidney disease. Previous in vitro studies found retention in the endoplasmic reticulum as a common feature of all uromodulin mutant isoforms. Both in vitro and in vivo we found that mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein. Notably, mutant uromodulin excretion was detected in patients carrying uromodulin mutations. Thus, our results suggest that mutant uromodulin exerts a gain-of-function effect that can be exerted by both intra- and extracellular forms of the protein

Urinary secretion and extracellular aggregation of mutant uromodulin isoforms

Uromodulin is exclusively expressed in the thick ascending limb and is the most abundant protein secreted in urine where it is found in high-molecular-weight polymers. Its biological functions are still elusive, but it is thought to play a protective role against urinary tract infection, calcium oxalate crystal formation, and regulation of water and salt balance in the thick ascending limb. Mutations in uromodulin are responsible for autosomal-dominant kidney diseases characterized by defective urine concentrating ability, hyperuricemia, gout, tubulointerstitial fibrosis, renal cysts, and chronic kidney disease. Previous in vitro studies found retention in the endoplasmic reticulum as a common feature of all uromodulin mutant isoforms. Both in vitro and in vivo we found that mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein. Notably, mutant uromodulin excretion was detected in patients carrying uromodulin mutations. Thus, our results suggest that mutant uromodulin exerts a gain-of-function effect that can be exerted by both intra- and extracellular forms of the protein

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation

Lithium abundances for 185 main-sequence stars - Galactic evolution and stellar depletion of lithium

We present a survey of lithium abundances in 185 main- sequence field stars with Teff between 5600 and 6600 K and [Fe/H] from -1.4 to +0.2 based on high-resolution spectra of 130 stars and a reanalysis of data from Lambert et al. (1991). The survey takes advantage of improved ways of determining effective temperature, metallicity, mass and age, offering an opportunity to investigate the behaviour of Li as a function of these parameters. An interesting result is the presence of a large gap in the Li-Teff plane, which distinguishes `Hyades-like, Li-dip' stars from other stars. These Li-dip stars have a well-defined mass, which decreases with metallicity. Stars above the gap, when divided into four metallicity groups, may show a correlation between Li abundance and stellar mass, but with a large dispersion that cannot be explained by observational errors or differences in metallicity and age, which ranges from 1.5 to 15 Gyr. This suggests that Li depletion occurs early in stellar life and that other parameters, e.g. initial rotation velocity and/or the rate of angular momentum loss, affect the degree of depletion. A comparison of the distribution of stars in the Li-[Fe/H] plane with evolutionary models of Romano et al. (1999) suggests that novae are a major source for the Li production in the Galactic disk.Comment: 11 pages, 8 figures, to appear in A&