Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Interaction between acrylic substrates and RAD16-I peptide in its self-assembling

[EN] Self-assembling peptides (SAP) are widely used as scaffolds themselves, and recently as fillers of microporous scaffolds, where the former provides a cell-friendly nanoenvironment and the latter improves its mechanical properties. The characterization of the interaction between these short peptides and the scaffold material is crucial to assess the potential of such a combined system. In this work, the interaction between poly(ethyl acrylate) (PEA) and 90/10 ethyl acrylate-acrylic acid copolymer P(EAcoAAc) with the SAP RAD16-I has been followed using a bidimensional simplified model. By means of the techniques of choice (congo red staining, atomic force microscopy (AFM), and contact angle measurements) the interaction and self-assembly of the peptide has proven to be very sensitive to the wettability and electro-negativity of the polymeric substrate.The authors acknowledge funding through the European Commission FP7 project RECATABI (NMP3-SL-2009-229239), and from the Spanish Ministerio de Ciencia e Innovacion through projects MAT2011-28791-C03-02 and -03. This work was also supported by the Spanish Ministerio de Educacion through M. Arnal-Pastor FPU 2009-1870 grant. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPV.Arnal Pastor, MP.; González-Mora, D.; García-Torres, F.; Monleón Pradas, M.; Vallés Lluch, A. (2016). Interaction between acrylic substrates and RAD16-I peptide in its self-assembling. Journal of Polymer Research. 23(9):173-184. https://doi.org/10.1007/s10965-016-1069-3S173184239Davis ME, Motion JP, Narmoneva DA, Takahashi T, Hakuno D, Kamm RD, Zhang S, Lee RT (2005) Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation 111(4):442–450Zhang S, Lockshin C, Cook R, Rich A (1994) Unusually stable beta-sheet formation in an ionic self-complementary oligopeptide. Biopolymers 34:663–672Zhang S, Altman M (1999) Peptide self-assembly in functional polymer science and engineering. Reac Func Polym 41:91–102Zhang S, Gelain F, Zhao X (2005) Designer self-assembling peptide nanofiber scaffolds for 3D tissue cell cultures. Semin Cancer Biol 15(5):413–420Zhang S, Zhao X, Spirio L, PuraMatrix (2005) Self-assembling peptide nanofiber scaffolds. In: Ma PX, Elisseeff J (eds) Scaffolding in tissue Engineering. CRC Press, Boca Raton, FL, pp. 217–238Sieminski AL, Semino CE, Gong H, Kamm RD (2008) Primary sequence of ionic self-assembling peptide gels affects endothelial cell adhesion and capillary morphogenesis. J Biomed Mater Res A 87(2):494–504Quintana L, Fernández Muiños T, Genove E, Del Mar Olmos M, Borrós S, Semino CE (2009) Early tissue patterning recreated by mouse embryonic fibroblasts in a three-dimensional environment. Tissue Eng Part A 15(1):45–54Garreta E, Genové E, Borrós S, Semino CE (2006) Osteogenic differentiation of mouse embryonic stem cells and mouse embryonic fibroblasts in a three-dimensional self-assembling peptide scaffold. Tissue Eng 12(8):2215–2227Semino CE, Merok JR, Crane GG, Panagiotakos G, Zhang S (2003) Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds. Differentiation 71:262–270Thonhoff JR, Lou DI, Jordan PM, Zhao X, Compatibility WP (2008) Of human fetal neural stem cells with hydrogel biomaterials in vitro. Brain Res 1187:42–51Tokunaga M, Liu ML, Nagai T, Iwanaga K, Matsuura K, Takahashi T, Kanda M, Kondo N, Wang P, Naito AT, Komuro I (2010) Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction. J Mol Cell Cardiol 49(6):972–983Takei J (2006) 3-Dimensional cell culture scaffold for everyone: drug screening. Tissue engineering and cancer biology. AATEX 11(3):170–176McGrath AM, Novikova LN, Novikov LN, Wiberg MBD (2010) ™ PuraMatrix™ peptide hydrogel seeded with Schwann cells for peripheral nerve regeneration. Brain Res Bull 83(5):207–213Wang W, Itoh S, Matsuda A, Aizawa T, Demura M, Ichinose S, Shinomiya K, Tanaka J (2008) Enhanced nerve regeneration through a bilayered chitosan tube: The effect ofintroduction of glycine spacer into the CYIGSR sequence. J Biomed Mater Res Part A 85:919–928Sargeant TD, Guler MO, Oppenheimer SM, Mata A, Satcher RL, Dunand DC, Stupp SI (2008) Hybrid bone implants: self-assembly of peptide amphiphile nanofibers within porous titanium. Biomaterials 29(2):161–171Vallés-Lluch A, Arnal-Pastor M, Martínez-Ramos C, Vilariño-Feltrer G, Vikingsson L, Castells-Sala C, Semino CE, Monleón Pradas M (2013) Combining self-assembling peptide gels with three-dimensional elastomer scaffolds. Acta Biomater 9(12):9451–9460Valles-Lluch A, Arnal-Pastor M, Martinez-Ramos C, Vilarino-Feltrer G, Vikingsson L, Monleon Pradas M (2013) Grid polymeric scaffolds with polypeptide gel filling as patches for infarcted tissue regeneration. Conf Proc IEEE Eng Med Biol Soc 2013:6961–6964Soler-Botija C, Bagó JR, Llucià-Valldeperas A, Vallés-Lluch A, Castells-Sala C, Martínez-Ramos C, Fernández-Muiños T, Chachques JC, Monleón Pradas M, Semino CE, Bayes-Genis A (2014) Engineered 3D bioimplants using elastomeric scaffold, self-assembling peptide hydrogel, and adipose tissue-derived progenitor cells for cardiac regeneration. Am J Transl Res 6(3):291–301Martínez-Ramos M, Arnal-Pastor M, Vallés-Lluch A, Monleón Pradas M (2015) Peptide gel in a scaffold as a composite matrix for endothelial cells. J Biomed Mater Res Part A 103 A:3293–3302Rico P, Rodríguez Hernández JC, Moratal D, Altankov G, Monleón Pradas M, Salmerón-Sánchez M (2009) Substrate-induced assembly of fibronectin into networks: influence of surface chemistry and effect on osteoblast adhesion. Tissue Eng Part A 15(11):3271–3281Gugutkov D, Altankov G, Rodríguez Hernández JC, Monleón Pradas M, Salmerón Sánchez M (2010) Fibronectin activity on substrates with controlled -OH density. J Biomed Mater Res A 92(1):322–331Rodríguez Hernández JC, Salmerón Sánchez M, Soria JM, Gómez Ribelles JL, Monleón Pradas M (2007) Substrate chemistry-dependent conformations of single laminin molecules on polymer surfaces are revealed by the phase signal of atomic force microscopy. Biophys J 93(1):202–207Cantini M, Rico P, Moratal D, Salmerón-Sánchez M (2012) Controlled wettability, same chemistry: biological activity of plasma-polymerized coatings. Soft Matter 8:5575–5584Anselme K, Ponche A, Bigerelle M (2010) Relative influence of surface topography and surface chemistry on cell response to bone implant materials. Part 2: biological aspects. Proc Inst Mech Eng H J Eng Med 224:1487–1507Hartgerink JD, Beniash E, Stupp SI (2002) Peptide-amphiphile nanofibers: a versatile scaffold for the preparation of self-assembling materials. Proc Natl Acad Sci U S A 99(8):5133–5138Busscher HJ, Vanpelt AWJ, Deboer P, Dejong HP, Arends J (1984) The effect of surface roughening of polymers on measured contact angles of liquids. Colloids Surf 9:319–331Birdi, KS. (1997) Surface tension of polymers. In: Yildrim Erbil H, ed. Handbook of surface and colloid chemistry CRC Press, Boca Raton, p. 292.Collier JH (2003) MessersmithPB.Enzymatic modification of self-assembled peptide structures with tissue transglutaminase. Bioconjug Chem 14(4):748–755Kakiuchi Y, Hirohashi N, Murakami-Murofushi K (2013) The macroscopic structure of RADA16 peptide hydrogel stimulates monocyte/macrophage differentiation in HL60 cells via cholesterol synthesis. BiochemBiophys Res Commun 433(3):298–304Pérez-Garnes M, González-García C, Moratal D, Rico P, Salmerón-Sánchez M (2011) Fibronectin distribution on demixednanoscale topographies. Int J Artif Organs 34(1):54–63Salmerón-Sánchez M, Rico P, Moratal D, Lee TT, Schwarzbauer JE, García AJ (2011) Role of material-driven fibronectin fibrillogenesis in cell differentiation. Biomaterials 32(8):2099–2105Ye Z, Zhang H, Luo H, Wang S, Zhou Q, DU X, et al. (2008) Temperature and pH effects on biophysical and morphological properties of self-assembling peptide RADA16-I. J Pept Sci 14:152–162Keselowsky BG, Collard DM, García AJ (2004) Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. Biomaterials 25:5947–5954Scotchford CA, Gilmore CP, Cooper E, Leggett GJ, Downes S (2002) Protein adsorption and human osteoblast-like cell attachment and growth on alkylthiol on gold self-assembled monolayers. J Biomed Mater Res 59:84–99Coelho NM, González-García C, Planell JA, Salmerón-Sánchez M, Altankov G (2010) Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction. Eur Cell Mater 19:262–272Briz N, Antolinos-Turpin CM, Alió J, Garagorri N, Gómez Ribelles JL, Gómez-Tejedor JA (2013) Fibronectin fixation on poly(ethyl acrylate)-based copolymers. J Biomed Mater Res B Appl Biomater 101(6):991–997Owens DK, Wendt RC (1969) Estimation of the surface free energy of polymers. J Appl Polym Sci 13(8):1741–1747Soria JM, Martínez Ramos C, Bahamonde O, García Cruz DM, Salmerón Sánchez M, García Esparza MA, Casas C, Guzmán M, Navarro X, Gómez Ribelles JL, García Verdugo JM, Monleón Pradas M, Barcia JA (2007) Influence of the substrate's hydrophilicity on the in vitro Schwann cells viability. J Biomed Mater Res A 83(2):463–470Van Krevelen, DW. (1997) Properties of polymers. Chapter 13 mechanical properties of solid polymers. Elsevier, pp. 367–43

Executive function and IQ predict mathematical and attention problems in very preterm children

Objective of this study was to examine the impact of executive function (EF) on mathematical and attention problems in very preterm (gestational age ≤ 30 weeks) children. Participants were 200 very preterm (mean age 8.2 ± 2.5 years) and 230 term children (mean age 8.3 ± 2.3 years) without severe disabilities, born between 1996 and 2004. EFs assessed included verbal fluency, verbal working memory, visuospatial span, planning, and impulse control. Mathematics was assessed with the Dutch Pupil Monitoring System and parents and teachers rated attention problems using standardized behavior questionnaires. The impact of EF was calculated over and above processi

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Idiotype vaccines for lymphoma therapy

Despite having been the first cancer vaccine to provide clear-cut evidence of biological and clinical efficacy as well as of clinical benefit in humans, idiotype vaccines have failed to become the first therapeutic cancer vaccine to be granted regulatory approval. Indeed, idiotypic vaccination is still an experimental therapeutic option for some types of B-cell malignancy over 20 years after its first use in patients with lymphoma. The ultimate reason for this situation lies in the recent failure of three large-scale, independent, randomized trials to achieve their respective main clinical end points. Interestingly, each trial had been designed with intrinsic pitfalls that are likely to have influenced, and perhaps even entirely compromized, all chances each study had to succeed. Therefore, it is difficult to conclude whether any of the different idiotype vaccines employed so far may still represent an ideal candidate for further trials. Meanwhile, other idiotype vaccine formulations are under active investigation

Idiotype vaccines for human B-cell malignancies

After twenty years of use in humans, customized idiotypic vaccination yet remains a non-approved, experimental therapeutic option for patients with lymphoma and myeloma. Potentially applicable to all B-cell malignancies whose cells express a clonal immunoglobulin or its epitopes on their surface, this treatment is designed to prevent disease recurrence or progression. Mostly used in follicular lymphoma patients so far, idiotype vaccines have clearly shown biological efficacy, clinical efficacy and clinical benefit in this setting, although no study aiming at regulatory approval of the procedure has been able to meet its main clinical endpoints. In mantle cell lymphoma, only biological efficacy has been proven for idiotypic vaccination, while in multiple myeloma a limited number of studies support the notion of biological and perhaps even clinical efficacy, although no credible evidence of clinical benefit has still emerged. Idiotype vaccines have been produced and administered in a number of substantially different manners. Therefore, the results of most clinical trials cannot be easily compared, and even less pooled together in meaningful meta-analyses. A more creative and yet scientifically sound way to design clinical trials of customized active immunotherapies will be key to the future development of idiotype vaccines, particularly considering that we currently lack any clinical or biological indicator to possibly predict which patients are more likely to respond to idiotypic vaccination from an immunologic point of view. This review aims at summarizing the multifaceted success achieved by idiotype vaccines, as well as at outlining the challenges awaiting them in the near future: how to improve feasibility, immunogenicity and efficacy, as well as how to confirm benefit and gain regulatory approval

Stem Cell Transplant and Idiotypic Vaccination for B-Cell Malignancies

Several types of B-cell malignancy, including but not limited to multiple myeloma and follicular lymphoma, are still considered incurable. In a substantial number of cases, patients must undergo either autologous or allogeneic stem cell transplantation as a standard of care procedure for their disease. Among experimental treatments for multiple myeloma and follicular lymphoma, idiotypic vaccination has been attempted over the last two decades with variable degrees of success. Few clinical trials have combined stem cell transplant procedures with idiotypic vaccination, and they are the subject of this review, which will also include some of our original data, as well as our overall evaluation of this field of clinical investigation. Although apparently at the opposite extremes of the therapeutic option array, toxicity-burdened stem cell transplantation and virtually innocuous idiotypic vaccination might well offer a sound curative opportunity to some patients with otherwise incurable B-cell malignancies, provided that the latter treatment first succeeds at obtaining regulatory approval

Stem Cell Transplant and Idiotypic Vaccination for B-Cell Malignancies

Several types of B-cell malignancy, including but not limited to multiple myeloma and follicular lymphoma, are still considered incurable. In a substantial number of cases, patients must undergo either autologous or allogeneic stem cell transplantation as a standard of care procedure for their disease. Among experimental treatments for multiple myeloma and follicular lymphoma, idiotypic vaccination has been attempted over the last two decades with variable degrees of success. Few clinical trials have combined stem cell transplant procedures with idiotypic vaccination, and they are the subject of this review, which will also include some of our original data, as well as our overall evaluation of this field of clinical investigation. Although apparently at the opposite extremes of the therapeutic option array, toxicity-burdened stem cell transplantation and virtually innocuous idiotypic vaccination might well offer a sound curative opportunity to some patients with otherwise incurable B-cell malignancies, provided that the latter treatment first succeeds at obtaining regulatory approval

Chapter 4: State and Trends of the World's Deserts

This chapter presents a panorama of the environmental status of the world deserts: their extent, location, uniqueness, vulnerability, the status of their natural resources, the trends of degradation related to land use and their impacts. Responses to land degradation are discussed at multiple level