Epoxy vitrimers incorporating physical crosslinks produced by self-association of alkyl chains

Epoxy vitrimers were synthesized employing stoichiometric amounts of diglycidyl ether of bisphenol A (DGEBA), sebacic acid (20% eq.) and an n-alkylamine, either octylamine (OA), dodecylamine (DA) or hexadecylamine (HA) (80% eq.). Apart from the chemical crosslinks generated by diester groups formed in transesterification reactions, these vitrimers include physical crosslinks arising from self-association of alkyl chains. The relative fraction and strength of physical crosslinks was high for octylamine (OA), intermediate for dodecylamine (DA) and low for hexadecylamine (HA). This was reflected by rubbery moduli that increased significantly from HA to OA. The covalently bonded tertiary amine generated in the epoxy-amine addition reaction was an efficient catalyst of transesterification reactions. Relatively fast stress relaxation rates were observed driven by transesterification reactions coupled to the dynamic exchange of self-associated alkyl chains. The occurrence of this last mechanism was evidenced by the stress relaxation observed for the linear polymer synthesized with stoichiometric amounts of DGEBA and OA that forms a permanent network up to temperatures close to degradation due to the presence of a high fraction of self-associated n-octyl chains. These vitrimers might find applications in several fields such as soft robotics, electro and magnetorheological elastomers, soft tissues and in additive manufacturing.Fil: Altuna, Facundo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Casado, Ulises Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Dell'Erba, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Luna, L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Hoppe, Cristina Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Williams, Roberto Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

Genome wide association scan for chronic periodontitis implicates novel locus

Background: There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).Methods: Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.Results: The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.Conclusions: Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. © 2014 Feng et al.; licensee BioMed Central Ltd

Reversible Dimerization/Polymerization of a Janus Diradical Producing Labile CC Bonds and Giant Chromism

En esta comunicación se presenta el estudio espectroscópico y téorico de la dimerización/oligomerización reversible de un birradical derivado de naftoditiofeno el cual en su forma monomérica presenta una intenso color azul mientras que al agregar se muestra incoloro, siendo éstas formas intercambiables gracias a la aplicación de estímulos débiles como presión o temperatura.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Engineering conductive protein films through nanoscale self-assembly and gold nanoparticles doping

Protein-based materials are usually considered as insulators, although conductivity has been recently shown in proteins. This fact opens the door to develop new biocompatible conductive materials. While there are emerging efforts in this area, there is an open challenge related to the limited conductivity of protein-based systems. This work shows a novel approach to tune the charge transport properties of protein-based materials by using electron-dense AuNPs. Two strategies are combined in a unique way to generate the conductive solid films: (1) the controlled self-assembly of a protein building block; (2) the templating of AuNPs by the engineered building block. This bottom-up approach allows controlling the structure of the films and the distribution of the AuNPs within, leading to enhanced conductivity. This work illustrates a promising strategy for the development of effective hybrid protein-based bioelectrical materialsThis work was partially supported by the European Research Council ERC-CoG-648071-ProNANO, ERC-PoC-841063-NIMM, Agencia Estatal de Investigación, Spain (PID2019- 111649RB-I00; and MAT2017-88693-R), and the Basque Government (Elkartek KK-2017/00008), E.L-M thanks the Spanish Ministry of Science and Innovation for the FPI grant (BES-2017-079646). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency – Grant No. MDM-2017-0720 (CIC biomaGUNE) and SEV-2016-0686 (IMDEA Nanociencia

A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection

Background: Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy. Methods: We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiretroviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and a plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter. Results: The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (388 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (65 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.57 episodes per 100 person-years). Conclusions: In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months

A fibrin coating method of polypropylene meshes enables the adhesion of menstrual blood-derived mesenchymal stromal cells: a new delivery strategy for stem cell-based therapies

Polypropylene (PP) mesh is well-known as a gold standard of all prosthetic materials of choice for the reinforcement of soft tissues in case of hernia, organ prolapse, and urinary incontinence. The adverse effects that follow surgical mesh implantation remain an unmet medical challenge. Herein, it is outlined a new approach to allow viability and adhesion of human menstrual blood-derived mesenchymal stromal cells (MenSCs) on PP surgical meshes. A multilayered fibrin coating, based on fibrinogen and thrombin from a commercial fibrin sealant, was optimized to guarantee a homogeneous and stratified film on PP mesh. MenSCs were seeded on the optimized fibrin-coated meshes and their adhesion, viability, phenotype, gene expression, and immunomodulatory capacity were fully evaluated. This coating guaranteed MenSC viability, adhesion and did not trigger any change in their stemness and inflammatory profile. Additionally, MenSCs seeded on fibrin-coated meshes significantly decreased CD4+ and CD8+ T cell proliferation, compared to in vitro stimulated lymphocytes (p < 0.0001). Hence, the proposed fibrin coating for PP surgical meshes may allow the local administration of stromal cells and the reduction of the exacerbated inflammatory response following mesh implantation surgery. Reproducible and easy to adapt to other cell types, this method undoubtedly requires a multidisciplinary and translational approach to be improved for future clinical uses.This work was supported by: SANTANDER BANK: “Convenio de colaboración empresarial en actividades de interés general” to F.M.; FUNDAÇÃO PARA A CIÊNCIA E A TECNOLOGIA (FCT): post-doctoral contract CEECIND/01026/2018 to J.M.S.; INSTITUTO DE SALUD CARLOS III (ISCIII): a “PFIS” contract (FI19/00041) to M.Á.P., a “Sara Borrell” grant (CD19/00048) to E.L.; a “Miguel Servet I” grant (MS17/00021), co-funded by the European Social Fund (ESF) “Investing in your future”, and projects CP17/00021 and PI18/0911, co-funded by the European Regional Development Fund (ERDF) “A way to make Europe” to J.G.C.; a “CIBERCV” grant (CB16/11/00494), co-funded by the ERDF to F.M.S.-M; JUNTA DE EXTREMADURA, CONSEJERÍA DE ECONOMÍA, CIENCIA Y AGENDA DIGITAL: project IB20184 (co-funded by ERDF) to E.L. and M.P.; grant GR18199, co-funded by the ERDF, to F.M.S.-M.; contracts TA18054 to I.J. and TA18011 to J.J.L. (cofinanced by FEDER)

Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 +/- 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved

Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy

Fingerprints of Through-Bond and Through-Space Exciton and Charge π-Electron Delocalization in Linearly Extended [2.2]Paracyclophanes

New stilbenoid and thiophenic compounds terminally functionalized with donor–donor, acceptor–acceptor, or donor–acceptor moieties and possessing a central [2.2]­paracyclophane unit have been prepared, and their properties interpreted in terms of through-bond and through space π-electron delocalization (i.e., π-conjugations). Based on photophysical data, their excited-state properties have been described with a focus on the participation of the central [2.2]­paracyclophane in competition with through-bond conjugation in the side arms. To this end, two-photon and one-photon absorption and emission spectroscopy, as a function of temperature, solvent polarity, and pressure in the solid state have been recorded. Furthermore, charge delocalization through the [2.2]­paracyclophane in the neutral state and in the oxidized species (radical cations, dications and radical trications) has been investigated, allowing the elucidation of the vibrational Raman fingerprint of through-space charge delocalization. Thus, a complementary approach to both “intermolecular” excitation and charge delocalizations in [2.2]­paracyclophane molecules is shown which can serve as models of charge and exciton migration in organic semiconductors