Caracterización de tintas de cemento de fosfato de calcio con adición de Poloxámero 407 para su posible aplicación en impresión 3D

3D printing of biomaterials is a growing technology in the manufacture of grafts suitable for the repair of bone defects with complex geometries. Calcium phosphate cements (CFC) are bioceramics used in orthopedic medicine due to their similarity to the mineral phase of bone, the ability to be molded as a paste and to harden in situ. The 3D printing of CFC would potentialize their application by allowing reconstructive surgeries of defects with complex geometries, however, a limitation is the low injectability of CFCs due to the phase separation that occurs during the injection of the paste. In this work, the implementation of a thermosensitive polymer such as Poloxamer 407 has been studied to generate an injectable ink. Such ink has been formulated to contain 5% of carbonated hydroxyapatite type B as a biocompatible and biodegradable nucleating agent. Additions of 0 %, 20 % and 40 % Wt aqueous solutions of Poloxamer 407 were evaluated as gel phase at a liquid/powder ratio of 0.75 mL/g. The injectability coefficient, the cohesion of the inks and the compressive strength of the cements using Weibull´s analysis were implemented, determining that the addition of polymer decreases the mechanical properties of the CFC by 52.68 % and 81.23 %, respectively with relation to the control CFC (0%), attributed to a lower densification of the cement. It was concluded that the additions of Poloxamer 407 do not interfere in the precipitation of calcium-deficient hydroxyapatite nor in the in vitro degradation of cements and favors the ink behavior for its possible implementation in 3D printing.La impresión 3D de biomateriales es una tecnología de gran auge para la fabricación de injertos aptos para la reparación de defectos óseos con geometrías complejas. Los cementos de fosfato de calcio (CFC) son biocerámicos empleados en la medicina ortopédica debido a su similitud con la fase mineral del hueso, la capacidad para ser moldeados como una pasta y endurecer in situ. La impresión 3D de CFC potencializaría su aplicación al permitir cirugías reconstructivas de defectos con geometrías complejas, sin embargo, una limitante es la baja inyectabilidad de los CFC debido a la separación de fases que ocurre durante la inyección de la pasta. En este trabajo se ha estudiado la implementación de un polímero termosensible como el Poloxámero 407 para generar una tinta inyectable. Dicha tinta ha sido formulada para contener 5 % de hidroxiapatita carbonatada tipo B como agente nucleante biocompatible y biodegradable. Se evaluaron adiciones de soluciones acuosas de Poloxámero 407 al 0 %, 20 % y 40 % en peso como fase gel a una relación líquido/polvo de 0,75 mL/g. Se determinó el coeficiente de inyectabilidad, la cohesión de las tintas y se caracterizó la resistencia a la compresión de los cementos empleando análisis Weibull, determinado que la adición de polímero disminuye las propiedades mecánicas de los CFC en un 52,68 % y 81,23 %, respectivamente, en relación con el CFC de control (0%), atribuido a una menor densificación del cemento. Se concluyó que las adiciones del Poloxámero 407 no interfieren en la precipitación de hidroxiapatita deficiente en calcio ni en la degradación in vitro de los cementos y favorece el comportamiento de la tinta para su posible implementación en impresión 3D

Pretreatment of urine samples with SDS improves direct identification of urinary tract pathogens with matrix-assisted laser desorption ionization-time of flight mass spectrometry

[EN]We pretreated with SDS 71 urine samples with bacterial counts of >10(5) CFU/ml and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) identification scores of <2, in order to minimize failure rates. Identification improved in 46.5% of samples, remained unchanged in 49.3%, and worsened in 4.2%. The improvement was more evident for Gram-negative (54.3%) than for Gram-positive (32%) bacteria

Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions

<p>Abstract</p> <p>Background</p> <p>The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4⁺, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4⁺cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions.</p> <p>Methods</p> <p>27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4⁺count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4⁺cell count to < 350/μL.</p> <p>Results</p> <p>After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4⁺cell count to < 350/μL. Patients with a CD4⁺nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to <it>Mycobacterium tuberculosis </it>purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4⁺cell count to < 350/μL.</p> <p>Conclusion</p> <p>Both the number (CD4⁺nadir) and the functional activity of CD4⁺(lymphoproliferative response to PPD) predict the CD4⁺decrease associated with discontinuation of ART in patients with controlled viremia.</p

Revista de Vertebrados de la Estación Biológica de Doñaña

Comportamiento reproductor del camaleón común (Chamaeleo chamaeleon L.) en el sur de EspañaDistribución de los reptiles en la provincia de Granada (SE. Península Ibérica)Datos sobre la reproducción y el crecimientode Psammodromus hispanicus Fitzinger, 1826 en un medio adehesado de la España CentralVariación en la colocación y orientación del nido del Alzacola (Cercotrichas galactotes) en dos especies de árbolesOrganización de la comunidad de aves reproductora en las landas montanas del País Vasco AtlánticoEcología de una población ibérica de lobos (Canis Lupus)Etude biométrique des Crosidures (Soricidae, Insectivora) de la región de Massa (Souss, Maroe).Variación geográfica del género Eliomys en la Península IbéricaTendencias gregarias del Ciervo (Cervus elaphus) en Doñana.Data on the autumn diet of the red deer (Cervus elaphus L. 1758) in the Montes de Toledo (Central Spain)Nota sobre la coexistencia de Hyla arborea (L. 1758E Hyla meridionalis (Boettger 1874) rn rl Valle del TiétarCalendario reproductivo y tamaño de las puesta en el galápago leproso, Mauremys leprosa (Shweigger, 1812), en Doñana, HuelvaPelícola (Felicola) inaqualis Piager, 1880 (MALLOPHAGA:TRICHODECTIDAE) parásito deE Herpestes ichneumon L (CARNIVORA: HERPESTIDAE)Abundancia y amplitud de los desplazamientos de Apodemus sylvaticus en cuatro biotopos de Doñana que difieren en cobertura vegetalPeer reviewe

The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans

Abstract The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires’ disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires’ disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. Trial registration ClinicalTrials.gov DRKS00005274, German Clinical Trials Register Author summary Interferons (IFNs) and pro-inflammatory cytokines are key regulators of gene expression and antibacterial defense during Legionella pneumophila infection. Here we demonstrate that production of these mediators was largely or partly dependent on the cyclic GMP-AMP synthase (cGAS)-STING pathway in human and murine cells. Cells of individuals carrying the common HAQ allele of TMEM173/STING were strongly impaired in their ability to respond to L. pneumophila, bacterial DNA or cyclic dinucleotides (CDNs), whereas the R232H allele was only attenuated in sensing of exogenous CDNs. Importantly, cGAS and STING contributed to antibacterial defense in mice during L. pneumophila lung infection, and the allele frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires’ disease patients as compared to healthy controls. Hence, sensing of bacterial DNA by the cGAS/STING pathway contributes to antibacterial defense against L. pneumophila infection, and the hypomorphic variant HAQ TMEM173/STING is associated with increased susceptibility to Legionnaires’ disease in humans

Escala del impacto de los síntomas percibidos en la esquizofrenia. Escala PRISS.

Objetivos Analizar las propiedades psicométricas de la escala PRISS (Patient-Reported Impact of Symptoms in Schizophrenia), que evalúa el impacto de las experiencias subjetivas en personas con esquizofrenia. Metodología La PRISS mide la presencia, frecuencia, preocupación e interferencia en la vida diaria de las experiencias subjetivas relacionadas con los principales síntomas que presentan las personas con esquizofrenia. Se realizó un estudio transversal en 162 pacientes diagnosticados de esquizofrenia, en España. El análisis psicométrico incluyó la fiabilidad test-retest, la consistencia interna y la validez estructural y convergente. Resultados La escala PRISS, de 28 ítems, mostró una buena fiabilidad test-retest ya que el 64,3% de los valores del coeficiente de correlación intraclase estuvieron entre 0,40 y 0,79, los cuales fueron estadísticamente significativos (p < 0,01). El análisis de la validez estructural reveló una estructura de tres factores, (1) experiencias productivas, (2) experiencias afectivo-negativas y (3) excitación, que representaron el 56,11% de la varianza. El factor 2 (experiencias afectivo-negativas) fue el que presentó una mejor consistencia interna. Los resultados del coeficiente de correlación Kappa entre la Escala de Síndrome Positivo y Negativo (PANSS) y la PRISS fue de 0,21 a 0,40 para la mitad de los ítems y entre 0,01 a 0,20 para la otra mitad. Los coeficientes de correlación de Pearson analizados entre la PRISS y la PANSS, la Escala para la Evaluación de Síntomas Negativos (SANS) y la Evaluación de Discapacidad de la Organización Mundial de la Salud (OMS-DAS) fueron estadísticamente significativos (p < 0,05) en el 72,2%. Conclusiones Nuestros resultados indican que la PRISS es una escala breve, fiable y válida para medir experiencias subjetivas en esquizofrenia y proporciona información valiosa complementaria a la evaluación clínica realizada por los profesionales.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Knowledge, attitudes and preventive practices of primary health care professionals towards alcohol use: A national, cross-sectional study.

Introduction Primary care (PC) professionals' knowledge about alcohol use has been identified as one of the barriers PC providers face in their clinic. Both PC professionals’ level of training and attitude are crucial in the clinical practice regarding alcohol use. Objective To evaluate the knowledge, attitude, and preventive practices of Spanish PC physicians and nurses towards alcohol use. Design An observational, descriptive, cross-sectional, multi-center study. Methodology Location: PC centers of the Spanish National Health System (NHS). Participants: PC physicians and nurses selected randomly from health care centers, and by sending an e-mail to semFYC and SEMERGEN members. Healthcare providers completed an online survey on knowledge, attitude, and follow-up recommendations for reducing alcohol intake. A descriptive, bivariate, and multivariate statistical analysis was conducted (p<0.05). Results Participants: 1,760 healthcare providers completed the survey (75.6% [95% CI 73.5–77.6] family physicians; 11.4% [95% CI 9.9–12.9] medical residents; and 12.5% [95% CI 10.9–14.1] nurses), with a mean age of 44.7 (SD 11.24, range: 26–64, 95% CI: 47.2–48.2). Knowledge was higher in family physicians (p<0.001), older professionals (Spearman's r = 0.11, p<0.001), and resident trainers (p<0.001). The PC professional most likely to provide advice for reducing alcohol use was: a nurse (p <0.001), female (p = 0.010), between 46 and 55 years old (p <0.001). Conclusions PC providers’ knowledge and preventive practices regarding alcohol use are scarce, hence specific training strategies to increase their knowledge and improve their attitude and skills with regard to this health problem should be considered a healthcare policy priority.post-print507 K

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world

Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice

BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern european populations

Genome-wide association studies have successfully identified 20 colorectal cancer susceptibility loci. Amongst these, four of the signals are defined by tagging single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4 and BMP2, respectively). By investigating these four SNPs in an initial cohort of Spanish origin, we found substantial evidence that minor allele frequencies (MAFs) may be different in northern and southern European populations. Therefore, we genotyped three additional southern European cohorts comprising a total of 2028 cases and 4273 controls. The meta-analysis results show that only one of the association signals (rs961253) is effectively replicated in the southern European populations, despite adequate power to detect all four. The other three SNPs (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and linkage disequilibrium patterns between northern and southern European cohorts. We hypothesize that this lack of replication could be the result of differential tagging of the functional variant in both sets of populations. Were this true, it would have complex consequences in both our ability to understand the nature of the real causative variants, as well as for further study designs