Radiation and Dust Sensor for Mars Environmental Dynamic Analyzer Onboard M2020 Rover.

The Radiation and Dust Sensor is one of six sensors of the Mars Environmental Dynamics Analyzer onboard the Perseverance rover from the Mars 2020 NASA mission. Its primary goal is to characterize the airbone dust in the Mars atmosphere, inferring its concentration, shape and optical properties. Thanks to its geometry, the sensor will be capable of studying dust-lifting processes with a high temporal resolution and high spatial coverage.

European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)-COST action 15111-from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.

Factors associated with the intensification of treatment in rheumatoid arthritis in clinical practice.

The aim of the present study was to analyse the patterns of treatment adjustment in rheumatoid arthritis (RA) patients with active disease in routine clinical care. This was a cross-sectional study of consecutive patients with RA conducted in five hospitals. Activity scales (DAS28-ESR) and function (HAQ) were measured, as well as whether ultrasound was performed as part of the assessment.

Adjustment in the clinical practice of treat-to-target guidelines for rheumatoid arthritis: Results of the ToARCan study.

Objective: To analyze compliance with t2t clinical practice guidelines.

Methods: Cross-sectional observational study in consecutive patients with rheumatoid arthritis (RA) in 5 hospitals in the Canary Islands. Patients filled out activity scales, HAQ and answered the question of whether the doctor had explained the treatment target.

Transgenic nematodes as biosensors for metal stress in soil pore water samples.

Caenorhabditis elegans strains carrying stress-reporter green fluorescent protein transgenes were used to explore patterns of response to metals. Multiple stress pathways were induced at high doses by most metals tested, including members of the heat shock, oxidative stress, metallothionein (mtl) and xenobiotic response gene families. A mathematical model (to be published separately) of the gene regulatory circuit controlling mtl production predicted that chemically similar divalent metals (classic inducers) should show additive effects on mtl gene induction, whereas chemically dissimilar metals should show interference.

[Management of needed health care workers in primary care. Automating the calculation].

The Santa Coloma de Gramenet Primary Care Service has designed a new tool to standardize and automate the process of planning the number of needed health care workers. The tool is divided in two parts: a calculator, which gives guidance on the foreseeable risk depending on the activity and the health care workers' workload, and sentinel indicators; the main is the "welfare basic level", that is the percentage structure of visited patients and their delay at 2, 3 and 7 calendar days, assessing the impact on the care of the population. The results of its use in the summer of 2010 have demonstrated its efficiency by lowering the needed workers with respect to 2009, achieving a better distribution according to the workload and improving the economic management.

Multidisciplinary management of soft tissue sarcomas.

Musculoskeletal sarcomas are a heterogeneous group of malignant neoplasms derived from connective tissue. Sarcomas represent about 1% of cancer in adults. The annual incidence in adults in Europe is around 14,000 new cases of soft tissue sarcomas (STS) and 4,800 new cases of bone sarcomas.

Phase II study of biweekly plitidepsin as second-line therapy in patients with advanced malignant melanoma.

The objective of this study was to evaluate the antitumor activity and safety profile of 5 mg/m2 plitidepsin administered as a 3-h continuous intravenous infusion every 2 weeks to patients with advanced malignant melanoma who relapsed or progressed after one line of systemic therapy. Objective response rate (primary efficacy endpoint) was evaluated according to Response Evaluation Criteria In Solid Tumors and toxicity was assessed using National Cancer Institute -Common Toxicity Criteria Version 2.0.

Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group.

Background: Few randomised studies have compared intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa).

Objective: To determine whether intermittent therapy is associated with a shorter time to progression.

Design, Setting, And Participants: 766 patients with locally advanced or metastatic PCa received a 3-mo induction treatment.

Preorganization of the hydroxyethylene dipeptide isostere: the preferred conformation in solution resembles the conformation bound to BACE.

Conformational analysis in solution of beta-secretase inhibitors 1 and 2 by NMR spectroscopy reveals that the hydroxyethylene isostere, an apparently flexible fragment widely used as a scissile bond replacement in aspartic protease inhibitors, exists in one predominant conformation in solution. This preferred conformation is similar to that adopted by the hydroxyethylene core of 1 in complex with beta-secretase and that adopted by hydroxyethylene cores of related compounds when bound to aspartic proteases, indicating that this structural unit is preorganized in solution.

Macrocyclic peptidomimetic inhibitors of beta-secretase (BACE): first X-ray structure of a macrocyclic peptidomimetic-BACE complex.

The synthesis of novel macrocyclic peptidomimetic inhibitors of the enzyme BACE1 is described. These macrocycles are derived from a hydroxyethylene core structure. Compound 7 was co-crystallized with BACE1 and the X-ray structure of the complex elucidated at 1.

Phase I and pharmacokinetic study of aplidine, a new marine cyclodepsipeptide in patients with advanced malignancies.

Purpose: To establish the safety, pharmacokinetic parameters, maximum-tolerated dose, and recommended dose of aplidine, a novel marine cyclodepsipeptide, in patients with advanced cancer.

Patients And Methods: Using a modified Fibonacci method, we performed a phase I and pharmacokinetic study of aplidine administered as a 24-hour intravenous infusion every 2 weeks.

Results: Sixty-seven patients received aplidine at a dose ranging from 0.

Dipeptides as effective prodrugs of the unnatural amino acid (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), a selective group II metabotropic glutamate receptor agonist.

(+)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (1), also known as LY354740, is a highly potent and selective agonist for group II metabotropic glutamate receptors (mGlu receptors 2 and 3) tested in clinical trials.

Age-associated oxidative damage leads to absence of gamma-cystathionase in over 50% of rat lenses: relevance in cataractogenesis.

Oxidative damage to lens proteins and glutathione depletion play a major role in the development of senile cataract. We previously found that a deficiency in gamma-cystathionase activity may be responsible for glutathione depletion in old lenses. The aims of this study were: (1) to investigate the mechanism that causes the age-related deficiency in gamma-cystathionase activity in the eye lens, and (2) to determine the role of gamma-cystathionase deficiency in cataractogenesis.

Biochemical and kinetic characterization of BACE1: investigation into the putative species-specificity for beta- and beta'-cleavage sites by human and murine BACE1.

Beta-amyloid peptides (Abeta) are produced by a sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. The lack of Abeta production in beta-APP cleaving enzyme (BACE1)(-/-) mice suggests that BACE1 is the principal beta-secretase in mammalian neurons. Transfection of human APP and BACE1 into neurons derived from wild-type and BACE1(-/-) mice supports cleavage of APP at the canonical beta-secretase site.

2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents.

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.

4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity.

The first potent inhibitors of glutamate racemase (MurI) enzyme that show whole cell antibacterial activity are described. Optically pure 4-substituted D-glutamic acid analogues with (2R,4S) stereochemistry and bearing aryl-, heteroaryl-, cinnamyl-, or biaryl-methyl substituents represent a novel class of glutamate racemase inhibitors. Exploration of the D-Glu core led to the identification of lead compounds (-)-8 and 10.