HIV/STI co-infection among men who have sex with men in Spain

In Spain, neither the HIV nor the STI national surveillance systems collect information on HIV/STI co-infection. However, there are two networks based on HIV/STI clinics which gather this data. We describe HIV prevalence in men who have sex with men (MSM) diagnosed with infectious syphilis and/or gonorrhoea in 15 STI clinics; and concurrent diagnoses of STI in MSM newly diagnosed with HIV in 19 HIV/STI clinics. In total, 572 MSM were diagnosed with infectious syphilis and 580 with gonorrhoea during 2005-2007. HIV prevalence among syphilis and gonorrhoea cases was 29.8% and 15.2% respectively. In the multivariate analysis, HIV/syphilis co-infection was associated with being Latin American; having a history of STI; reporting exclusively anal intercourse; and having sex with casual or several types of partners. HIV and gonorrhoea co-infection was associated with age older than 45 years; having no education or only primary education completed; and having a history of STI. In total, 1,462 HIV infections were newly diagnosed among MSM during 2003-2007. Of these, 31.0% were diagnosed with other STI at the same time. Factors associated with STI co-infection among new HIV cases in MSM were being Latin American; and having sex with casual partners or with both steady and casual partners. In Spain, a considerable proportion of MSM are co-infected with HIV and STI.This work was funded by two grants (36646/07; 36794/08) from the Foundation for Research and Prevention of AIDS in Spain (Fundación para la Investigación y la Prevención del SIDA en España–FIPSE).S

Anisotropic micro-sphere-based finite elasticity applied to blood vessel modelling

A fully three-dimensional anisotropic elastic model for vascular tissue modelling is here presented. The underlying strain energy density function is assumed to additively decouple into volumetric and deviatoric contributions. A straightforward isotropic neo-Hooke-type law is used to model the deviatoric response of the ground substance, whereas a micro-structurally or rather micro-sphere-based approach will be employed to model the contribution and distribution of fibres within the biological tissue of interest. Anisotropy was introduced by means of the use of von Mises orientation distribution functions. Two different micro-mechanical approaches -- a, say phenomenological, exponential ansatz and a worm-like-chain-based formulation -- are applied to the micro-fibres and illustratively compared. The passage from micro-structural contributions to the macroscopic response is obtained by a computational homogenisation scheme, namely numerical integration over the surface of the individual micro-spheres. The algorithmic treatment of this integration is discussed in detail for the anisotropic problem at hand, so that several cubatures of the micro-sphere are tested in order to optimise the accuracy at reasonable computational cost. Moreover, the introduced material parameters are identified from simple tension tests on human coronary arterial tissue for the two micro-mechanical models investigated. Both approaches are able to recapture the experimental data. Based on the identified sets of parameters, we first discuss a homogeneous deformation in simple shear to evaluate the models' response at the micro-structural level. Later on, an artery-like two-layered tube subjected to internal pressure is simulated by making use of a non-linear finite element setting. This enables to obtain the micro- and macroscopic responses in an inhomogeneous deformation problem, namely a blood-vessel-representative boundary value problem. The effect of residual stresses is additionally included in the model by means of a multiplicative decomposition of the deformation gradient tensor which turns out to crucially affect the simulation results

On the use of non-linear transformations for the evaluation of anisotropic rotationally symmetric directional integrals. Application to the stress analysis in fibred soft tissues

Microsphere-based constitutive models are a helpful tool in the modelling of materials with a microstructure composed of contributing elements directionally arranged. This is the case, for instance, for fibred soft tissues. In these models, the macroscopic mechanical behaviour is obtained from the integration of the micro-structural contribution of each component (e.g. each fibre) over the surface of an underlying microsphere, which allows incorporating the mechanical features of the micro-constituents to the macroscopic response. The combination of this sort of models and the associated numerical techniques constitutes a powerful modelling tool for which an efficient integration scheme is required. In this regard, the unit sphere discretizations proposed by Bazant and Oh (ZAMM-J Appl Math Mech Z Angew Math Mech 1986; 66(1):37-49) have been used for the integration of the microscopic contributions in isotropic materials. Nevertheless, the inclusion of anisotropy has important implications with regard to the integration scheme, since very fine discretizations are needed to perform the integration accurately, causing the integration process to be very costly. In addition, the storage of internal variables at each integration direction of every integration point is required for constitutive models based on the use of internal variables at the micro-structural level, which renders this approach rather complex and memory demanding. In order to reduce the number of necessary integration directions, several non-linear transformations for the integration of rotationally symmetric functions over the Surface of the unit sphere are here presented. Their accuracy in the integration of the von Mises orientation distribution function is evaluated. Furthermore, a hyperelastic microsphere-based constitutive law for the modelling of soft biological tissues is used in order to check the accuracy and computational efficiency of the proposed transformations within a Finite Element context in inhomogeneous deformation problems. Simulation results show the suitability of the proposed methodology in order to accurately approximate the Value of the integrals within reasonable computational costs. Copyright (C) 2009 John Wiley & Sons, Ltd

Article connexin 50 expression in ependymal stem progenitor cells after spinal cord injury activation

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Ion channels included in the family of Connexins (Cx) help to control cell proliferation and differentiation of neuronal progenitors. Here we explored the role of Connexin 50 (Cx50) in cell fate modulation of adult spinal cord derived neural precursors located in the ependymal canal (epSPC). epSPC from non-injured animals showed high expression levels of Cx50 compared to epSPC from animals with spinal cord injury (SCI) (epSPCi). When epSPC or epSPCi were induced to spontaneously differentiate in vitro we found that Cx50 favors glial cell fate, since higher expression levels, endogenous or by over-expression of Cx50, augmented the expression of the astrocyte marker GFAP and impaired the neuronal marker Tuj1. Cx50 was found in both the cytoplasm and nucleus of glial cells, astrocytes and oligodendrocyte-derived cells. Similar expression patterns were found in primary cultures of mature astrocytes. In addition, opposite expression profile for nuclear Cx50 was observed when epSPC and activated epSPCi were conducted to differentiate into mature oligodendrocytes, suggesting a different role for this ion channel in spinal cord beyond cell-to-cell communication. In vivo detection of Cx50 by immunohistochemistry showed a defined location in gray matter in non-injured tissues and at the epicenter of the injury after SCI. epSPCi transplantation, which accelerates locomotion regeneration by a neuroprotective effect after acute SCI is associated with a lower signal of Cx50 within the injured area, suggesting a minor or detrimental contribution of this ion channel in spinal cord regeneration by activated epSPCi

Purinergic receptors in spinal cord-derived ependymal stem/progenitor cells and their potential role in cell-based therapy for spinal cord injury

© 2015 Cognizant Comm. Corp. Spinal cord injury (SCI) is a major cause of paralysis with no current therapies. Following SCI, large amounts of ATP and other nucleotides are released by the traumatized tissue leading to the activation of purinergic receptors that, in coordination with growth factors, induce lesion remodeling and repair. We found that adult mammalian ependymal spinal cord-derived stem/progenitor cells (epSPCs) are capable of responding to ATP and other nucleotidic compounds, mainly through the activation of the ionotropic P2X4, P2X7, and the metabotropic P2Y1 and P2Y4 purinergic receptors. A comparative study between epSPCs from healthy rats versus epSPCis, obtained after SCI, shows a downregulation of P2Y1 receptor together with an upregulation of P2Y4 receptor in epSPCis. Moreover, spinal cord after severe traumatic contusion shows early and persistent increases in the expression of P2X4 and P2X7 receptors around the injury, which are completely reversed when epSPCis were ectopically transplanted. Since epSPCi transplantation significantly rescues neurological function after SCI in parallel to inhibition of the induced P2 ionotropic receptors, a potential avenue is open for therapeutic alternatives in SCI treatments based on purinergic receptors and the endogenous reparative modulation

Effects of region of birth, educational level and age on late presentation among men who have sex with men newly diagnosed with HIV in a network of STI/HIV counselling and testing clinics in Spain

This paper analyses late presentation (LP) of HIV infection, and its determinants, among men who have sex with men (MSM) in Spain, newly diagnosed with HIV (2003-2011) in 15 sexually transmitted infection/HIV counselling and testing clinics. LP was defined as  12 months before diagnosis (12-24 months (aOR:1.4; 95% CI:1.0-2.0); > 24 months (aOR:2.2; 95% CI:1.7-3.0)). LP was less likely in MSM reporting a known HIV-infected partner as infection source or symptoms compatible with acute retroviral syndrome. 'Region of birth' interacted with 'educational level' and 'steady partner as infection source': only African and Latin-American MSM with low educational level were more likely to present late; Latin-American men attributing their infection to steady partner, but no other MSM, had LP more frequently. In Spain, HIV testing among MSM should be promoted, especially those > 34 years old and migrants with low educational level. The current recommendation that MSM be tested at least once a year is appropriate.This work has been supported with grants No. 36303/02, 36537/05 and 36794/08 from FIPSE (Fundación para la Investigación y la Prevención del Sida en España). The authors wish to thank Kathy Fitch for the English review.S

A rationally designed self-immolative linker enhances the synergism between a polymer-rock inhibitor conjugate and neural progenitor cells in the treatment of spinal cord injury.

Rho/ROCK signaling induced after spinal cord injury (SCI) contributes to secondary damage by promoting apoptosis, inflammation, and axon growth inhibition. The specific Rho-kinase inhibitor fasudil can contribute to functional regeneration after SCI, although inherent low stability has hampered its use. To improve the therapeutic potential of fasudil, we now describe a family of rationally-designed bioresponsive polymer-fasudil conjugates based on an understanding of the conditions after SCI, such as low pH, enhanced expression of specific proteases, and a reductive environment. Fasudil conjugated to poly-l-glutamate via a self-immolative redox-sensitive linker (PGA-SS-F) displays optimal release kinetics and, consequently, treatment with PGA-SS-F significantly induces neurite elongation and axon growth in dorsal root ganglia explants, spinal cord organotypic cultures, and neural precursor cells (NPCs). The intrathecal administration of PGA-SS-F after SCI in a rat model prevents early apoptosis and induces the expression of axonal growth- and neuroplasticity-associated markers to a higher extent than the free form of fasudil. Moreover, a combination treatment comprising the acute transplantation of NPCs pre-treated with PGA-SS-F leads to enhanced cell engraftment and reduced cyst formation after SCI. In chronic SCI, combinatory treatment increases the preservation of neuronal fibers. Overall, this synergistic combinatorial strategy may represent a potentially efficient clinical approach to SCI treatment

Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment

Altres ajuts: Fundació Marató TV3 2017/refs.20172230, 20172231 i 20172110We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesen-chymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that al-lows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment pro-tected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccha-ride-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments