Marine Alkaloid 2,2-Bis(6-bromo-3-indolyl) Ethylamine and Its Synthetic Derivatives Inhibit Microbial Biofilms Formation and Disaggregate Developed Biofilms

The antimicrobial activity of the marine bisindole alkaloid 2,2-bis(6-bromo-3-indolyl) ethylamine (1) and related synthetic analogues (compounds 2–8) against target microorganisms was investigated by Minimum Inhibitory Concentration (MIC) determination. Compound 1 showed the greatest antimicrobial activity with the lowest MIC (8 mg/L) against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae, while the derivatives exhibited higher MICs values (from 16 to 128 mg/L). Compounds 1, 3, 4, and 8, the most active ones, were then tested against E. coli, S. aureus, K. pneumoniae, and Candida albicans during biofilms formation as well as on 24 h developed biofilms. The natural alkaloid 1 inhibited the biofilm formation of all the tested microorganisms up to 82.2% and disaggregated biofilms of E. coli, S. aureus, K. pneumoniae, and C. albicans after 30 min of contact, as assessed by viable plate count and crystal violet (CV) staining (optical density at 570 nm). Synthetic derivatives 3, 4, and 8 displayed anti-biofilm activity toward individual bacterial populations. This study highlights the potential of marine bisindole alkaloid 1 as anti-biofilm agent and shows, through a preliminary structure activity relationship (SAR), the importance of halogens and ethylamine side chain for the antimicrobial and antibiofilm activities of this bisindole series

Synthesis and Evaluation of Saccharide-Based Aliphatic and Aromatic Esters as Antimicrobial and Antibiofilm Agents

A small library of sugar-based (i.e., glucose, mannose and lactose) monoesters containing hydrophobic aliphatic or aromatic tails were synthesized and tested. The antimicrobial activity of the compounds against a target panel of Gram-positive, Gram-negative and fungi was assessed. Based on this preliminary screening, the antibiofilm activity of the most promising molecules was evaluated at different development times of selected food-borne pathogens (E. coli, L. monocytogenes, S. aureus, S. enteritidis). The antibiofilm activity during biofilm formation resulted in the following: mannose C10 > lactose biphenylacetate > glucose C10 > lactose C10. Among them, mannose C10 and lactose biphenylacetate showed an inhibition for E. coli 97% and 92%, respectively. At MICs values, no toxicity was observed on Caco-2 cell line for all the examined compounds. Overall, based on these results, all the sugar-based monoesters showed an interesting profile as safe antimicrobial agents. In particular, mannose C10 and lactose biphenylacetate are the most promising as possible biocompatible and safe preservatives for pharmaceutical and food applications

Processi ed innovazioni nel settore delle tecnologie out of autoclave per materiali compositi

Visto il crescente interesse nei confronti dei materiali compositi, per le numerose applicazioni e i vantaggi che offrono, stanno conoscendo notevole sviluppo le tecnologie Out of Autoclave (OoA). Esse sono alternative all'autoclave, che richiede tempi, costi e risorse maggiori, nonché ha una minore flessibilità. Le tecnologie OoA, invece, sono più rapide e meno costose, e stanno raggiungendo livelli di qualità e prestazioni molto vicini a quelli dell'autoclave. Questo elaborato presenta alcune delle innovazioni di maggior interesse, raggruppate per settori: processi, materiali e strutture dei laminati

Basal cell carcinoma: 10-year experience with electrochemotherapy

BACKGROUND: Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. METHODS: In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. RESULTS: Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age 6469 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p 64 0.001). CONCLUSIONS: One or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation. Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

A holistic study of the WLCG energy needs for the LHC scientific program

The WLCG infrastructure provides the compute power and storage capacity needed by the Large Hadron Collider (LHC) experiments at CERN. The infrastructure is distributed across over 170 data centres in more than 40 countries. The amount of energy consumed by the WLCG to support the scientific program of the LHC experiments, and its evolution, depends on different factors: the luminosity of the LHC and its operating conditions; the data volume and the data complexity; the evolving computing models and the offline software of the experiments; the ongoing R&D program in preparation for the next LHC phase (HL-LHC); the evolution of computing hardware technology towards better energy efficiency; and the modernization of the facilities hosting the data centres to improve Power Usage Effectiveness. This contribution presents a study of the WLCG energy needs and their potential evolution during the future LHC program based on the factors mentioned above. Some of the information is obtained from the CERN experience but then extrapolated to the whole of WLCG. The study provides, therefore, a holistic view for the infrastructure rather than a detailed prediction at the level of the individual facilities. It presents a clear view of the trends and offers a model for more refined studies

Synthesis and Biological Characterization of the New Glycolipid Lactose Undecylenate (URB1418)

As a follow-up to our previous studies on glycolipid surfactants, a new molecule, that is lactose 6'-O-undecylenate (URB1418), was investigated. To this end, a practical synthesis and studies aimed at exploring its specific properties were carried out. URB1418 showed antifungal activities against Trichophyton rubrum F2 and Candida albicans ATCC 10231 (MIC 512 μg/mL) and no significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. At the same time, it presented anti-inflammatory properties, as documented by the dose-dependent reduction in LPS-induced NO release in RAW 264.7 cells, while a low antioxidant capacity in the range of concentrations tested (EC50 &gt; 200 µM) was also observed. Moreover, URB1418 offers the advantage of being more stable than the reference polyunsaturated lactose esters and of being synthesized using a "green" procedure, involving an enzymatic method, high yield and low manufacturing cost. For all these reasons and the absence of toxicity (HaCaT cells), the new glycolipid presented herein could be considered an interesting compound for applications in various fields

Catecholamine-induced Takotsubo syndrome: a case series

Background: Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during the acute phase, good short-term prognosis, and frequent apical sparing at echocardiogram. We present two clinical cases of cat-TS treated in our department. Case summary: Case one: 78-year-old man, admitted to Ear Nose and Throat Unit for surgical removal of oral squamous cellular carcinoma. During surgery, the occurrence of hypotensive episode was treated with catecholamines. After surgery, the occurrence of atrial fibrillation was followed by evidence of phasic increase of troponin levels and akinesia of midventricular segments. Angiography showed the absence of significant coronary stenoses, and during hospital stay, we observed rapid recovery of wall motion abnormalities. Case two: 64-year-old woman, admitted for hysteropexy surgery, during which cardiac arrest occurred, treated with epinephrine i.v.1 mg and DC shock. Two hours after resuscitation, the patient developed pulmonary oedema, troponin levels increased progressively, and the echocardiogram demonstrated hypokinesia in all midventricular segments with apical sparing. Afterwards, an urgent angiography highlighted normal coronary anatomy. Cardiac magnetic resonance imaging (MRI) revealed oedema corresponding to hypokinetic areas. On the seventh day, echocardiogram showed a complete remission of wall motion abnormalities. Discussion: These cases warn the physicians about the importance of routinely screening myocardial impairment through clinical assessment, electrocardiogram (ECG) monitoring, and serial cardiac troponin testing after catecholamine i.v. bolus administration. In case of alterations of these exams, performing a prompt echocardiogram allows early detection of cat-TS, to provide immediate suitable medical support and avoid complications

Implications for the use of acid preservatives in 24-hour urine for measurements of high demand biochemical analytes in clinical laboratories

Background: Evaluate the level of interference of biochemists dosages in the 24-hour urine using or not the 6 mol/l HCl acid in different concentrations and conditions and its implications in the most demanded analytes in clinical laboratory.Methods: Twenty-two volunteers collected three 24-hour urine in 3 conditions: with 5 ml/l and 20 ml/l of 6 mol/l HCl in the container, and without acid preservative. the samples collected without preservative were separated in aliquots and added 5 ml/l of 6 mol/l HCl after 24 h. Analytes, uric acid creatinine, urea, chlorides, glucose, magnesium, sodium, potassium, microalbumin, proteins, amylase, aldosterone, calcium, cortisol, phosphorus, citric acid, oxalate, and metanephrines, were determined.Results: Uric acid, glucose, microalbumin, protein, amylase and aldosterone showed that %CV ranging from 16 to 57% in the presence of acid preservative. Analytes that need acid preservative cortisol, citric acid and oxalate showed %CV ranging from 6 to 27% with r=0.66, r=0.77, r=0.70 respectively provided 5 ml/l after delivery and r=0.31, r=0.70 and r=0.48 without preservative acid when compared with the gold standard (with 20 ml/l of 6 mol/l HCl).Conclusions: Glucose, microalbumin, protein, amylase and aldosterone urinary did not show good performance in the presence of acid preservative. Analytes that need acid preservative showed variation acceptable in condition 5 ml/l of 6 mol/l HCl added after 24 h. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Associacao Fundo de Pesquisa a Psicobiologia (AFIP)Universidade Federal de São Paulo, Dept Psicobiol, UNIFESP, BR-04024002 São Paulo, BrazilAssoc Fundo Incent Psicofarmacol, AFIP Med Diagnost, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, UNIFESP, BR-04024002 São Paulo, BrazilWeb of Scienc

Lymphedema and nutrition: A review

Nutrition is considered a basic component in the management of any vascular disease. Lymphedema is characterised by an increase of interstitial fluid due to a lymphatic system morphological and/or functional alteration. Therapeutic management of lymphedema includes a multi-faceted approach based on compression and physiotherapy mainly. Weight control and antiinflammatory and anti-edema diet are two additional necessary components of the holistic therapy in presence of primary or secondary limb lymphedema. This narrative review provides the available information derived from the scientific literature on nutrition in lymphedema, which anyway lacks robust evidence. Additional information and speculations are provided on the role of food, diet, nutraceuticals and fasting on the basic processes at the root of the chronic progressive degeneration of tissue lymph stasis, i.e. weight excess, inflammation, edema, fibroadiposis. More targeted and randomized studies are needed in order to assess and standardise the obvious, so far neglected, role of nutrition in lymphedema patients

New detailed characterization of the residual luminescence emitted by the GAGG:Ce scintillator crystals for the HERMES Pathfinder mission

The HERMES (High Energy Rapid Modular Ensemble of Satellites) Pathfinder mission aims to develop a constellation of nanosatellites to study astronomical transient sources, such as gamma-ray bursts, in the X and soft $\gamma$ energy range, exploiting a novel inorganic scintillator. This study presents the results obtained describing, with an empirical model, the unusually intense and long-lasting residual emission of the GAGG:Ce scintillating crystal after irradiating it with high energy protons (70 MeV) and ultraviolet light ($\sim$ 300 nm). From the model so derived, the consequences of this residual luminescence for the detector performance in operational conditions has been analyzed. It was demonstrated that the current generated by the residual emission peaks at 1-2 pA, thus ascertaining the complete compatibility of this detector with the HERMES Pathfinder nanosatellites