Development of Electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Monolayers Containing Eugenol and Their Application in Multilayer Antimicrobial Food Packaging

[EN] In this research, different contents of eugenol in the 2.5-25 wt.% range were first incorporated into ultrathin fibers of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) by electrospinning and then subjected to annealing to obtain antimicrobial monolayers. The most optimal concentration of eugenol in the PHBV monolayer was 15 wt.% since it showed high electrospinnability and thermal stability and also yielded the highest bacterial reduction against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This eugenol-containing monolayer was then selected to be applied as an interlayer between a structural layer made of a cast-extruded poly(3-hydroxybutyrate) (PHB) sheet and a commercial PHBV film as the food contact layer. The whole system was, thereafter, annealed at 160°C for 10 s to develop a novel multilayer active packaging material. The resultant multilayer showed high hydrophobicity, strong adhesion and mechanical resistance, and improved barrier properties against water vapor and limonene vapors. The antimicrobial activity of the multilayer structure was also evaluated in both open and closed systems for up to 15 days, showing significant reductions (R ¿ 1 and < 3) for the two strains of food-borne bacteria. Higher inhibition values were particularly attained against S. aureus due to the higher activity of eugenol against the cell membrane of Gram positive (G+) bacteria. The multilayer also provided the highest antimicrobial activity for the closed system, which better resembles the actual packaging and it was related to the headspace accumulation of the volatile compounds. Hence, the here-developed multilayer fully based on polyhydroxyalkanoates (PHAs) shows a great deal of potential for antimicrobial packaging applications using biodegradable materials to increase both quality and safety of food products.This research was funded by the Spanish Ministry of Science and Innovation (MICI) through the RTI2018-097249-B-C21 program number and the H2020 EU project YPACK (reference number 773872). KF-L is a recipient of a Santiago Grisolía (Ref. 0001426013N810001A201) research contract of the Valencian Government (GVA) whereas ST-G holds a Juan de la Cierva¿ Incorporación contract (IJCI-2016-29675) from MICI. The authors would also like to thank the Unidad Asociada IATA-UJI Plastics Technology.Figueroa-López, KJ.; Cabedo, L.; Lagaron, JM.; Torres Giner, S. (2020). Development of Electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Monolayers Containing Eugenol and Their Application in Multilayer Antimicrobial Food Packaging. 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Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we report the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populationsWe acknowledge the support by Uvigo Marine Research Centre funded by the “Excellence in Research (INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union through the ERDF Operational Programme Galicia 2014-2020. This work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a predoctoral (FPI) grant from Ministerio de Economía y Competitividad, SpainS

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Kinetics and Adsorption Equilibrium in the Removal of Azo-Anionic Dyes by Modified Cellulose

This study introduces a new and bio-friendly adsorbent based on natural and cetyltrimethy-lammonium chloride (CTAC)-modified adsorbent prepared from wheat straw residues for the removal of Congo red (CR) and tartrazine azo-anionic dyes from aqueous solution. The adsorbent was characterized by thermogravimetric analysis (TGA), calorimetric differential (DSC), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDX), and pH point of zero charge (pHPZC) techniques. It was found that decreasing the adsorbent dose and increasing the initial concentration favors the removal of tartrazine and Congo red. Tartrazine adsorption capacities were 2.31 mg/g for the cellulose extracted from wheat residues (WC) and 18.85 mg/g for the modified wheat residue cellulose (MWC) for tartrazine as well as 18.5 mg/g for WC and 19.92 for MWC during Congo red (CR) adsorption, respectively. Increasing the initial and decreasing the adsorbent dose concentration favored the adsorption process. From time effect analysis, it was found that the equilibrium time was reached at 120 min when modified wheat cellulose was used and at 480 min when wheat cellulose was used. The kinetics of adsorption were described by pseudo-second-order in all cases with R2 > 0.95. The obtained data equilibrium from this research was well-fitted by the Freundlich isotherm model.This research received no external funding.Peer reviewe

Development of Multilayer Ciprofloxacin Hydrochloride Electrospun Patches for Buccal Drug Delivery

Bacterial infections in the oral cavity can become a serious problem causing pain, sores and swelling for several weeks. This type of infection could be alleviated using mucoadhesive delivery systems, allowing local administration of the antibiotic to inhibit bacterial spreading. This work reports the development of a multilayer antibiotic patch containing ciprofloxacin hydrochloride (CPX)-loaded electrospun fibers for the treatment of such infections. For this, the release kinetics of the CPX-loaded fibers was modulated using different ratios of polyester blends. The selected reservoir layer was analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), wide angle x-ray scattering (WAXS) and differential scanning calorimetry (DSC). These analyses confirmed the presence and good distribution of the drug in the fibers and that the drug is in an amorphous state within the reservoir layer. To enhance mucoadhesion whilst ensuring drug directionality, the reservoir layer was assembled to a backing and an adhesive layer. This multilayer patch was assessed in terms of in vitro drug release, adhesion and antimicrobial properties. The multilayer strategy showed excellent antimicrobial properties over time and also a strong adhesion patch time in the volunteers for an average of 7 h. These results highlight the capabilities of multilayer electrospun patches as platforms to treat oral infections.This research was funded by the Spanish Ministry of Science and Universities (project RTI-2018-097249-B-C21), the Valencian Innovation Agency BIOENCAP project (reference number INNCAD00-18-31), the H2020 EU projects FODIAC (reference number 778388), CAPSULTEK (reference number 873827), the CYTED thematic network (code 319RT0576) and BIOINICIA’s internal project ASOPHARM.Peer reviewe

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD\u2013Atrial Fibrillation (GARFIELD-AF). Among 17\ua0168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (\ub1antiplatelet therapy) at enrolment, and of these patients, 5066 with 653 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70\ua0905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56\ub70% vs 49\ub78%; median, 59\ub77% vs 50\ub70%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0\ub7860 [0\ub7852\u20130\ub7867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0\ub7829 [0\ub7821\u20130\ub7837]). The difference between FIR and TTR explained 17\ub74% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably