Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Antibiotic resistance is at dangerous levels and increasing worldwide. The search for new antimicrobial drugs to counteract this problem is a priority for health institutions and organizations, both globally and in individual countries. Sarconesiopsis magellanica blowfly larval excretions and secretions (ES) are an important source for isolating antimicrobial peptides (AMPs). This study aims to identify and characterize a new S. magellanica AMP. RP-HPLC was used to fractionate ES, using C18 columns, and their antimicrobial activity was evaluated. The peptide sequence of the fraction collected at 43.7 min was determined by mass spectrometry (MS). Fluorescence and electronic microscopy were used to evaluate the mechanism of action. Toxicity was tested on HeLa cells and human erythrocytes; physicochemical properties were evaluated. The molecule in the ES was characterized as sarconesin II and it showed activity against Gram-negative (Escherichia coli MG1655, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa PA14) and Gram-positive (Staphylococcus aureus ATCC 29213, Micrococcus luteus A270) bacteria. The lowest minimum inhibitory concentration obtained was 1.9 µM for M. luteus A270; the AMP had no toxicity in any cells tested here and its action in bacterial membrane and DNA was confirmed. Sarconesin II was documented as a conserved domain of the ATP synthase protein belonging to the Fli-1 superfamily. The data reported here indicated that peptides could be alternative therapeutic candidates for use in infections against Gram-negative and Gram-positive bacteria and eventually as a new resource of compounds for combating multidrug-resistant bacteria. © 2019 by the authors

Changes in multimorbidity and polypharmacy patterns in young and adult population over a 4-year period: A 2011–2015 comparison using real-world data

The pressing problem of multimorbidity and polypharmacy is aggravated by the lack of specific care models for this population. We aimed to investigate the evolution of multimorbidity and polypharmacy patterns in a given population over a 4-year period (2011–2015). A cross-sectional, observational study among the EpiChron Cohort, including anonymized demographic, clinical and drug dispensation information of all users of the public health system ≥65 years in Aragon (Spain), was performed. An exploratory factor analysis, stratified by age and sex, using an open cohort was carried out based on the tetra-choric correlations among chronic diseases and dispensed drugs during 2011 and compared with 2015. Seven baseline patterns were identified during 2011 named as: mental health, respiratory, allergic, mechanical pain, cardiometabolic, osteometabolic, and allergic/derma. Of the epidemiological patterns identified in 2015, six were already present in 2011 but a new allergic/derma one appeared. Patterns identified in 2011 were more complex in terms of both disease and drugs. Results confirmed the existing association between age and clinical complexity. The systematic associations between diseases and drugs remain similar regarding their clinical nature over time, helping in early identification of potential interactions in multimorbid patients with a high risk of negative health outcomes due to polypharmacy

Search for Early Gamma-ray Production in Supernovae Located in a Dense Circumstellar Medium with the Fermi LAT

Supernovae (SNe) exploding in a dense circumstellar medium (CSM) are hypothesized to accelerate cosmic rays in collisionless shocks and emit GeV gamma rays and TeV neutrinos on a time scale of several months. We perform the first systematic search for gamma-ray emission in Fermi LAT data in the energy range from 100 MeV to 300 GeV from the ensemble of 147 SNe Type IIn exploding in dense CSM. We search for a gamma-ray excess at each SNe location in a one year time window. In order to enhance a possible weak signal, we simultaneously study the closest and optically brightest sources of our sample in a joint-likelihood analysis in three different time windows (1 year, 6 months and 3 months). For the most promising source of the sample, SN 2010jl (PTF10aaxf), we repeat the analysis with an extended time window lasting 4.5 years. We do not find a significant excess in gamma rays for any individual source nor for the combined sources and provide model-independent flux upper limits for both cases. In addition, we derive limits on the gamma-ray luminosity and the ratio of gamma-ray-to-optical luminosity ratio as a function of the index of the proton injection spectrum assuming a generic gamma-ray production model. Furthermore, we present detailed flux predictions based on multi-wavelength observations and the corresponding flux upper limit at 95% confidence level (CL) for the source SN 2010jl (PTF10aaxf).Comment: Accepted for publication in ApJ. Corresponding author: A. Franckowiak ([email protected]), updated author list and acknowledgement

Fermi observations of high-energy gamma-ray emission from GRB 090217A

The Fermi observatory is advancing our knowledge of Gamma-Ray Bursts (GRBs) through pioneering observations at high energies, covering more than 7 decades in energy with the two on-board detectors, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). Here we report on the observation of the long GRB 090217A which triggered the GBM and has been detected by the LAT with a significance greater than 9 sigma. We present the GBM and LAT observations and on-ground analyses, including the time-resolved spectra and the study of the temporal profile from 8 keV up to 1 GeV. All spectra are well reproduced by a Band model. We compare these observations to the first two LAT-detected, long bursts GRB 080825C and GRB 080916C. These bursts were found to have time-dependent spectra and exhibited a delayed onset of the high-energy emission, which are not observed in the case of GRB 090217A. We discuss some theoretical implications for the high-energy emission of GRBs.Comment: 17 pages, 4 figures. Contact Authors: Fred, Piron; Sara, Cutini; Andreas, von Kienli

Baseline drug treatments as indicators of increased risk of COVID-19 mortality in Spain and Italy

This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice

Fermi-LAT Study of Gamma-ray Emission in the Direction of Supernova Remnant W49B

We present an analysis of the gamma-ray data obtained with the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope in the direction of SNR W49B (G43.3-0.2). A bright unresolved gamma-ray source detected at a significance of 38 sigma is found to coincide with SNR W49B. The energy spectrum in the 0.2-200 GeV range gradually steepens toward high energies. The luminosity is estimated to be 1.5x10^{36} (D/8 kpc)^2 erg s^-1 in this energy range. There is no indication that the gamma-ray emission comes from a pulsar. Assuming that the SNR shell is the site of gamma-ray production, the observed spectrum can be explained either by the decay of neutral pi mesons produced through the proton-proton collisions or by electron bremsstrahlung. The calculated energy density of relativistic particles responsible for the LAT flux is estimated to be remarkably large, U_{e,p}>10^4 eV cm^-3, for either gamma-ray production mechanism.Comment: 9 pages, 10 figure

Initial therapy, regimen change, and persistence in a spanish cohort of newly treated type 2 diabetes patients: A retrospective, observational study using real-world data

The World Health Organization considers the non-adherence to medication a significant issue with global impact, especially in chronic conditions such as type 2 diabetes. We aim to study antidiabetic treatment initiation, add-on, treatment switching, and medication persistence. We conducted an observational study on 4247 individuals initiating antidiabetic treatment between 2013 and 2014 in the EpiChron Cohort (Spain). We used Cox regression models to estimate the likelihood of non-persistence after a one-year follow-up, expressed as hazard ratios (HRs). Metformin was the most frequently used first-line antidiabetic (80% of cases); combination treatment was the second most common treatment in adults aged 40–79 years, while dipeptidyl peptidase-4 inhibitors were the second most common in individuals in their 80s and over, and in patients with renal disease. Individuals initiated on metformin were less likely to present addition and switching events compared with any other antidiabetic. Almost 70% of individuals initiated on monotherapy were persistent. Subjects aged 40 and over (HR 0.53–0.63), living in rural (HR 0.79) or more deprived areas (HR 0.77–0.82), or receiving polypharmacy (HR 0.84), were less likely to show discontinuation. Our findings could help identify the population at risk of discontinuation, and offer them closer monitoring for proper integrated management to improve prognosis and health outcomes