Migration studies of two common components of UV-curing inks into food simulants

The Rapid Alert System for Food and Feed (RASFF) has reported many cases of different UV curing inks components in foodstuffs during the last few years. These contaminants reach foodstuffs mainly by set-off, their principal migration mechanism from the package. Under this premise, this work has tried to characterize the process of migration of two common UV ink components: a photoinitiator (4-Methylbenzophenone) and a coinitiator (Ethyl-4-(dimethylamino) benzoate), from the most common plastic material used in food packaging low-density polyethylene (LDPE) into six different food simulants. The migration kinetics tests were performed at four different common storage temperatures, obtaining the key migration parameters for both molecules: the coefficients of diffusion and partition. The migration process was highly dependent on the storage conditions, the photoinitiator properties and the pH of the foodstuff.This research was funded by Ministerio de Economía Y Competitividad Ref. No. AGL/2011-26531 “MIGRATIN” and Fondo Europeo de Desarrollo Regional (FEDER)S

Involvement of Raft Aggregates Enriched in Fas/CD95 Death-Inducing Signaling Complex in the Antileukemic Action of Edelfosine in Jurkat Cells

BACKGROUND: Recent evidence suggests that co-clustering of Fas/CD95 death receptor and lipid rafts plays a major role in death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: By a combination of genetic, biochemical, and ultrastructural approaches, we provide here compelling evidence for the involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein (FADD), and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine, the prototype compound of a promising family of synthetic antitumor lipids named as synthetic alkyl-lysophospholipid analogues. Co-immunoprecipitation assays revealed that edelfosine induced the generation of the so-called death-inducing signaling complex (DISC), made up of Fas/CD95, FADD, and procaspase-8, in lipid rafts. Electron microscopy analyses allowed to visualize the formation of raft clusters and their co-localization with DISC components Fas/CD95, FADD, and procaspase-8 following edelfosine treatment of Jurkat cells. Silencing of Fas/CD95 by RNA interference, transfection with a FADD dominant-negative mutant that blocks Fas/CD95 signaling, and specific inhibition of caspase-8 prevented the apoptotic response triggered by edelfosine, hence demonstrating the functional role of DISC in drug-induced apoptosis. By using radioactive labeled edelfosine and a fluorescent analogue, we found that edelfosine accumulated in lipid rafts, forming edelfosine-rich membrane raft clusters in Jurkat leukemic T-cells. Disruption of these membrane raft domains abrogated drug uptake and drug-induced DISC assembly and apoptosis. Thus, edelfosine uptake into lipid rafts was critical for the onset of both co-aggregation of DISC in membrane rafts and subsequent apoptotic cell death. CONCLUSIONS/SIGNIFICANCE: This work shows the involvement of DISC clusters in lipid raft aggregates as a supramolecular and physical entity responsible for the induction of apoptosis in leukemic cells by the antitumor drug edelfosine. Our data set a novel framework and paradigm in leukemia therapy, as well as in death receptor-mediated apoptosis

Simultaneous sleep study and nasoendoscopic investigation in a patient with obstructive sleep apnoea syndrome refractory to continuous positive airway pressure: a case report

<p>Abstract</p> <p>Introduction</p> <p>The standard treatment for obstructive sleep apnoea syndrome is nasal continuous positive airway pressure. In most cases the obstruction is located at the oropharyngeal level, and nasal continuous positive airway pressure is usually effective. In cases of non-response to nasal continuous positive airway pressure other treatments like mandibular advancement devices or upper airway surgery (especially bi-maxillary advancement) may also be considered.</p> <p>Case presentation</p> <p>We report the case of a 38-year-old Caucasian man with severe obstructive sleep apnoea syndrome, initially refractory to nasal continuous positive airway pressure (and subsequently also to a mandibular advancement devices), in which the visualization of the upper airway with sleep endoscopy and the concomitant titration of positive pressure were useful in the investigation and resolution of sleep disordered breathing. In fact, there was a marked reduction in the size of his nasopharynx, and a paresis of his left aryepiglotic fold with hypertrophy of the right aryepiglotic fold. The application of bi-level positive airway pressure and an oral interface successfully managed his obstructive sleep apnoea.</p> <p>Conclusion</p> <p>This is a rare case of obstructive sleep apnoea syndrome refractory to treatment with nocturnal ventilatory support. Visualization of the endoscopic changes, during sleep and under positive pressure, was of great value to understanding the mechanisms of refractoriness. It also oriented the therapeutic option. Refractoriness to obstructive sleep apnoea therapy with continuous positive airway pressure is rare, and each case should be approached individually.</p

Recommendations for the Treatment of Anti-Melanoma Differentiation-Associated Gene 5-positive Dermatomyositis-Associated Rapidly Progressive Interstitial Lung Disease

Objectives: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. Methods: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. Results: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. Conclusions: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.This project was supported by Spanish Rheumatology Society and Spanish Society of Internal Medicine (GEAS, Study Group on Autoimmune Diseases)

Zinc-Assisted Microscale Granules Made of the SARS-CoV-2 Spike Protein Trigger Neutralizing, Antivirus Antibody Responses

Altres ajuts: acords transformatius de la UABThe development of new and more efficient vaccination approaches is a constant need, due to the pressure of historical and emerging infectious diseases and the limited efficacy and universality of the current vaccination technologies. Peptides and recombinant proteins have been explored for decades as subunit vaccines for bacterial and viral infections, presented either as soluble protein species or as virus-like assemblies. Recently, synthetic secretory protein-only microscale granules have been developed as dynamic depots for sustained protein release. They are based on the reversible coordination between ionic Zn and histidine residues, which promotes a fast formation of granular particles in vitro out of soluble protein and a slow release of such building block protein in vivo through the physiological chelation of the metal. Such an endocrine-like platform represents a new drug delivery system fully validated in oncology by which soluble and functional protein drugs are progressively released from the granules and made available for antitumor activities upon subcutaneous administration. By exploring such an approach for immunization here, microparticles made of a recombinant form of the receptor binding domain (RBD) of SARS-CoV-2 were tested as an antigen delivery system for induction of antibody responses against the virus upon administration of the material in the absence of added adjuvants. Also, the comparison between protein materials produced in bacterial, mammalian, or insect cell factories has demonstrated a moderate impact of protein glycosylation on the final immunological performance of the system. Therefore, we propose the consideration of synthetic protein secretory granules as a new sustainable immunization platform based on fully manageable, self-organized, and self-formulated immunogens, aimed at reducing the dosage, costs, and complexity of vaccination regimens

Antigenic Proteins Involved in Occupational Rhinitis 1 and Asthma Caused by Obeche Wood (Triplochiton Scleroxylon)

Background Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated. Objective To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma Materials and methods An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies. Results Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA−), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases. Conclusions Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens

Snail1 factor behaves as a therapeutic target in renal fibrosis.

Kidney fibrosis is a devastating disease that leads to organ failure, and no specific treatment is available to preserve organ function. In fibrosis, myofibroblasts accumulate in the interstitium leading to massive deposition of extracellular matrix and organ disfunction. The origin of myofibroblasts is multiple and the contribution of renal epithelial cells after undergoing epithelial-to-mesenchymal transition (EMT) is still debated. In a model unable to reactivate the EMT inducer Snail1 upon damage, we show that Snail1 is required in renal epithelial cells for the development of fibrosis. Damage-mediated Snail1 reactivation induces a partial EMT that relays fibrotic and inflammatory signals to the interstitium through the activation of TGF-β and NF-B pathways. Snail1-induced fibrosis can be reverted in vivo and inhibiting Snail1 in a model of obstructive nephropathy highly ameliorates fibrosis. These results reconcile conflicting data on the role of EMT in renal fibrosis and provide avenues for the design of antifibrotic therapies.pre-print8435 K

Real Wage Responsiveness to Unemployment in Spain: Asymmetries Along the Business Cycle

We estimate real wage cyclicality in the period compressed between 1987 and 2013 using a large administrative dataset of workers in Spain. Real wages are weakly procyclical in Spain and focusing on differences in different phases of the business cycle, we find that differences across expansions and recessions are significant, with an even lower real wage cyclicality in recessions. Furthermore, higher levels of unemployment do not translate into additional real wages adjustments when the economy is contracting, while lower levels of unemployment during expansions have incremental effects on wage elasticity. This general result holds after accounting for differences in tenure, type of contract and age categories. Nevertheless, wages of newly-hired workers are the most sensitive to the business cycle and exhibit the lowest asymmetric pattern between expansions and recessions. At the other end, wages of workers with more than six years of tenure can be characterized as the most protected against economic downturns. The same is true for fixed-term vs. permanent workers, as well as for young vs. older workers

New Mutations in Chronic Lymphocytic Leukemia Identified by Target Enrichment and Deep Sequencing

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease without a well-defined genetic alteration responsible for the onset of the disease. Several lines of evidence coincide in identifying stimulatory and growth signals delivered by B-cell receptor (BCR), and co-receptors together with NFkB pathway, as being the driving force in B-cell survival in CLL. However, the molecular mechanism responsible for this activation has not been identified. Based on the hypothesis that BCR activation may depend on somatic mutations of the BCR and related pathways we have performed a complete mutational screening of 301 selected genes associated with BCR signaling and related pathways using massive parallel sequencing technology in 10 CLL cases. Four mutated genes in coding regions (KRAS, SMARCA2, NFKBIE and PRKD3) have been confirmed by capillary sequencing. In conclusion, this study identifies new genes mutated in CLL, all of them in cases with progressive disease, and demonstrates that next-generation sequencing technologies applied to selected genes or pathways of interest are powerful tools for identifying novel mutational changes