HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

Background HIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART. Go to: Methods We analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes. Go to: Results Immunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP. Go to: Conclusion Our results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset.Fondo de Investigación Sanitaria FIS PI14/01693 PI13/0796 PI16/0503Fondos Europeos para el Desarrollo Regional (FEDER) CTS2593Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo CTS2593AGAUR 2017SGR948GILEAD GLD14/293The Spanish AIDS Research Network of Excellence RD12/0017/0029 RD16/0025/0019 RD16/0025/0006Junta de Andalucía. Consejería de Salud y Bienestar Social C-0013-201

HIV-Infected Subjects With Poor CD4 T-Cell Recovery Despite Effective Therapy Express High Levels of OX40 and α4β7 on CD4 T-Cells Prior Therapy Initiation

BackgroundHIV-infected subjects with suboptimal CD4 restoration despite suppressive combined antiretroviral treatment (cART) (immunodiscordant subjects) have been classically characterized after a variable period of time under cART. Recently, we have reported that an increased frequency of proliferating CD4 T-cells in these subjects is already present before the cART onset. The potential contribution of peripheral compensatory homeostatic proliferation (HP) is yet unknown. We aimed to analyze the expression of HP-related cellular markers on CD4 T-cells of immunodiscordant subjects before cART.MethodsWe analyzed the expression of OX40 and α4β7 on peripheral CD4 T-cells from immunodiscordant and control subjects (n = 21 each group) before cART initiation, and also on available follow-up samples (after 24 month of suppressive cART). Additionally, we tested the expression of these markers in an in vitro system for the study of human HP processes.ResultsImmunodiscordant subjects showed increased levels of OX40 and α4β7 on CD4 T-cells before cART initiation. While the cART tended to reduce these levels, immunodiscordant subjects still maintained comparatively higher levels of OX40 and α4β7 after 24 months under suppressive cART. These HP-related markers were upregulated in vitro during the human HP, especially during the fast HP.ConclusionOur results are compatible with exacerbated HP processes in immunodiscordant subjects, already before the cART onset

Short time guided bone regeneration using beta-tricalcium phosphate with and without fibronectin. An experimental study in rats

 The aim of this histomorphometric study was to assess the bone regeneration potential of beta-tricalcium phosphate with fibronectin (β-TCP-Fn) in critical-sized defects (CSDs) in rats calvarial, to know whether Fn improves the new bone formation in a short time scope.  CSDs were created in 30 Sprague Dawley rats, and divided into four groups (2 or 6 weeks of healing) and type of filling β-TCP-Fn, β-TCP, empty control). Variables studied were augmented area (AA), gained tissue (GT), mineralized/non mineralized bone matrix (MBM/NMT) and bone substitute (BS). 60 samples at 2 and six weeks were evaluated. AA was higher for treatment groups comparing to controls (p < 0.001) and significant decrease in BS area in the β-TCP-Fn group from 2 to 6 weeks (p = 0.031). GT was higher in the β-TCP-Fn group than in the controls expressed in % (p = 0.028) and in mm2 (p = 0.011), specially at two weeks (p=0.056).  Both β-TCP biomaterials are effective as compared with bone defects left empty in maintaining the volume. GT in defects regeneration filed with β-TCP-Fn are significantly better in short healing time when comparing with controls but not for β-TCP used alone in rats calvarial CSDs

Nuevas localidades de especies interesantes en Doñana y la costa de Huelva (Sw España)

New floristic records of species for Doñana and Huelva (SW Spain) Palabras clave. Flora, Doñana, Calystegia soldanella, Herniaria cinerea, Trigonella monspeliaca, Viola lactea, Wolffia arrhiza, especies amenazadas.Key words. Flora, Doñana, Calystegia soldanella, Herniaria cinerea, Trigonella monspeliaca, Viola lactea, Wolffia arrhiza, threatened species

The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4(+) T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP(2)) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP(2) accumulation is increased in syntenin-1–depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP(2) production, and the dynamics of HIV-1 entry

Diagnóstico precoz de gestación en ovejas a partir de muestras de plasma sanguíneo analizadas mediante espectroscopia en el infrarrojo cercano (NIRS)

Se ha realizado un estudio para determinar si es posible diferenciar las ovejas gestantes de las vacías en un momento cercano a la inseminación analizando el plasma sanguíneo con la tecnología NIRS (Near-infrared reflectance spectroscopy) y comparar el grado de precisión del diagnóstico con la determinación de Pregnancy-Associated Glycoprotein (PAG) y de Progesterona (P4). Se tomaron muestras de sangre en 188 ovejas Rasa Aragonesa y Ansotana 18 y 25 días después de ser inseminadas. En el plasma recuperado, se analizó la concentración de PAG y de P4 mediante ELISA con kits comerciales y se determinó el espectro en un espectrofotómetro NIRS. La fertilidad de la IA fue del 47,9%. El día 18 el NIRS mostró una mayor sensibilidad para detectar las ovejas gestantes que la PAG (sensibilidad: 98,9 vs 32,2 %; P<0,001) y similar a la P4. La especificidad fue 100% en NIRS y PAG, mientras que la de la P4 fue menor (84,7; P<0,001). El día 25 no se encontraron diferencias en ningún parámetro entre NIRS y PAG. Se concluye que el NIRS es un método seguro de diagnóstico de gestación en ovejas a partir del día 18 de la fecundación y sin utilizar compuestos químicos.PublishedPremio "Mejores Trabajos sobre el sector de los Pequeños Rumiantes". Sección Grupos de Investigación. SEOC 201

Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving α4β1 integrin function

51 p.-7 fig.-1 tab.-2 fig.supl.Myeloma cell adhesion dependent on α4β1 integrin is crucial for the progression of multiple myeloma (MM). The α4β1-dependent myeloma cell adhesion is up-regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine-1-phosphate (S1P) regulates immune cell trafficking upon binding to G-protein-coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up-regulated the α4β1-mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high-affinity α4β1 that efficiently bound the α4β1 ligand VCAM-1, a finding that was associated with S1P-triggered increase in talin-β1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of α4β1-dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2-Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving α4β1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of α4β1-dependent adhesion and migration of myeloma cells by CXCL12-S1P combined activities might have important consequences for myeloma disease progressionThis study was supported by the Ministerio de Ciencia e Innovación (Grant Nos SAF2011-24022 to JT, SAF2009-07035 to AGP, SAF2009-11037 to AH, RD06/0020/0011 to JT and AGP, RD06/0020/0006 to NCG and MG and PI081825 to MG), the Comunidad de Madrid (Grant No. P2010/BMD-2314 to AGP, JT and AH) and the Fundación de Investigación Médica Mutua Madrileña (to AGP and MG). AH was also funded by the FP7-People-2009-RG (Grant No. 246655), a Ramón y Cajal Fellowship (Grant No. RYC-2007-00697) and the Pro-CNIC Foundation.Peer reviewe

Obstructive Sleep Apnoea Syndrome, Endothelial Function and Markers of Endothelialization. Changes after CPAP

Study objectives This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Design Observational study, before and after CPAP therapy. Setting and Patients We studied 30 patients with apnoea/hypopnoea index (AHI) > 15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. Measurements and results After three month with CPAP, FMD significantly increased (1072.26 +/- 483.21 vs. 1604.38 +/- 915.69 PU, p<0.005) cf-DNA and MPs significantly decreased (187.93 +/- 115.81 vs. 121.28 +/- 78.98 pg/ml, p<0.01, and 69.60 +/- 62.60 vs. 39.82 +/- 22.14 U/mu L, p<0.05, respectively) and VEGF levels increased (585.02 +/- 246.06 vs. 641.11 +/- 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p< 0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. Conclusions CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage

TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients

TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.This study is supported by grants from Instituto de Salud Carlos III (ISCIII) (grant # PI20CIII/00004 to S.R.). M.A.J.-S. and A.F.-R. are supported by “Instituto de Salud Carlos III” (grant # CP17CIII/00007 and CP14CIII/00010, respectively).S

EVALUACIÓN DEL PERFIL DEL ESPECIALISTA EN TRANSPORTE SUSTENTABLE EN MÉXICO

El transporte desempeña un papel clave y estratégico para el desarrollo de las actividades económicas, culturales y sociales de cualquier comunidad, ciudad, país o región. Los servicios de transporte ya sean de bienes o personas, para que puedan ser considerados de calidad deben poseer características como son: Seguridad, accesibilidad, confiabilidad, confort y sustentabilidad. Esta última característica, recientemente ha sido reconocida por organismos internacionales (Organización de las Naciones Unidas, Organización para la Cooperación y el Desarrollo Económico y Banco interamericano de Desarrollo), como un factor importante cuando se busca medir la competitividad de una localidad, país o región. De acuerdo a Sánchez y Wilmsmeier (2005) existe una relación positiva entre proporcionar una adecuada infraestructura de transporte y el crecimiento económico de un lugar, ya que permite ventajas importantes como generación de empleos, uso eficiente de recursos naturales, ahorros en tiempos de viaje, reducción de costos y una mejor salud para los habitantes