Data for all: Tactile graphics that light up with picture-perfect resolution.

People who are blind do not have access to graphical data and imagery produced by science. This exclusion complicates learning and data sharing between sighted and blind persons. Because blind people use tactile senses to visualize data (and sighted people use eyesight), a single data format that can be easily visualized by both is needed. Here, we report that graphical data can be three-dimensionally printed into tactile graphics that glow with video-like resolution via the lithophane effect. Lithophane forms of gel electropherograms, micrographs, electronic and mass spectra, and textbook illustrations could be interpreted by touch or eyesight at ≥79% accuracy (n = 360). The lithophane data format enables universal visualization of data by people regardless of their level of eyesight.

Empirical use of ß-lactam/ß-lactamase inhibitor combinations does not increase mortality compared with cloxacillin and cefazolin in methicillin-susceptible Staphylococcus aureus bacteraemia: a propensity-weighted cohort study.

OBJECTIVES: To evaluate the effectiveness of empirical therapy with ß-lactam/ß-lactamase inhibitor combinations (BL/BLICs) for MSSA bacteraemia. METHODS: We conducted a post hoc analysis of all adult patients with MSSA bacteraemia who were hospitalized at a Spanish university hospital between 2013 and 2018. We compared 30 day mortality among patients receiving initial therapy with BL/BLICs (de-escalated to cloxacillin or cefazolin within 96 h) versus cloxacillin or cefazolin, using propensity score analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: We evaluated 373 patients with MSSA bacteraemia. Among them, 198 patients met the eligibility criteria, including 127 patients in the BL/BLICs group and 71 patients in the cloxacillin/cefazolin group. Patients in the BL/BLICs group had a higher Charlson comorbidity index (median, 2 [IQR, 1-4.5] versus 2 [IQR, 0-4]); an increased proportion of high-risk sources (i.e. endocarditis, respiratory sources and bacteraemia of unknown origin [34.6% versus 18.3%]); and an earlier start of antibiotic treatment (median, 0 days [IQR, 0-0] versus 1 day [IQR, 1-2]). Thirty day mortality did not significantly differ between the BL/BLICs and the cloxacillin/cefazolin groups (27 patients [21.3%] versus 13 patients [18.3%]; IPTW-adjusted OR = 0.53 [95% CI, 0.18-1.51]). For secondary outcomes, 7 day mortality and 90 day relapse were not statistically different between study groups (8.7% versus 5.6% [P = 0.62] and 6.2% versus 3.8% [P = 0.81], respectively). CONCLUSIONS: BL/BLICs might be an effective empirical treatment for MSSA bacteraemia when de-escalated to cloxacillin or cefazolin within 96 h from the index blood culture.

Precision medicine in sepsis and septic shock: From omics to clinical tools.

Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.

Mortality in Staphylococcus aureus bacteraemia remains high despite adherence to quality indicators: secondary analysis of a prospective cohort study.

OBJECTIVES: To evaluate the association between compliance with previously published quality indicators (QIs) for the management of Staphylococcus aureus bacteraemia (SAB) and 30-day mortality. METHODS: We conducted a post hoc analysis of all adult patients with SAB who were hospitalized at a Spanish university hospital between 2013 and 2018. We evaluated the compliance with 7 QIs of SAB management (i.e., Infectious Diseases consultation, follow-up blood cultures, early source control, echocardiography, early cloxacillin or cefazolin, vancomycin monitoring, and appropriate treatment duration). The QIs compliance rate was considered good if ≥75% of the QIs recommended in each patient were performed. We studied the impact of different risk factors (including QIs compliance) on 30-day all-cause mortality adjusting by multivariable modeling and propensity-matched analysis. RESULTS: We included 441 patients with SAB. The QIs compliance rate was ≥75% in 361 patients (81.9%). A total of 95 patients (21.5%) died within 30 days after the index blood culture. In the multivariable model, the variables associated with 30-day mortality were: age (OR, 1.1; 95% CI, 1.0-1.1), Charlson comorbidity index (OR, 1.2; 95% CI, 1.1-1.4), persistent bacteraemia >72 h (OR, 6.0; 95% CI, 3.2-11.5), infective endocarditis (OR, 2.8; 95% CI, 1.2-6.7), and SAB of unknown source (OR, 3.3; 95% CI, 1.5-7.1). We did not find an association between a global QIs compliance rate of ≥75% or any individual QI with 30-day mortality. CONCLUSIONS: SAB 30-day mortality remains high despite good adherence to previously published QIs for the management of SAB. Future research should focus on additional factors to further improve SAB-related mortality.

Visualizing 3D imagery by mouth using candy-like models.

Handheld models help students visualize three-dimensional (3D) objects, especially students with blindness who use large 3D models to visualize imagery by hand. The mouth has finer tactile sensors than hand, which could improve visualization using microscopic models that are portable, inexpensive, and disposable. The mouth remains unused in tactile learning. Here, we created bite-size 3D models of protein molecules from "gummy bear" gelatin or nontoxic resin. Models were made as small as rice grain and could be coded with flavor and packaged like candy. Mouth, hands, and eyesight were tested at identifying specific structures. Students recognized structures by mouth at 85.59% accuracy, similar to recognition by eyesight using computer animation. Recall accuracy of structures was higher by mouth than hand for 40.91% of students, equal for 31.82%, and lower for 27.27%. The convenient use of entire packs of tiny, cheap, portable models can make 3D imagery more accessible to students.

Enhanced molecular typing and macrolide and tetracycline-resistance mutations of Treponema pallidum in Barcelona.

Aim: To describe the molecular types of Treponema pallidum and the proportion of macrolide and tetracycline resistance mutations in Barcelona. Materials & methods: Molecular type was determined using the Enhanced-CDC Typing system and antibiotic resistance was determined by sequencing the 23S and 16S rRNA genes. Results: A total of 183 patients were enrolled and 213 specimens (99 ulcers, 114 bloods) were collected. Sixty-two (70.5%) of 88 ulcers and 0 (0%) of bloods T. pallidum-DNA containing samples were fully typed. Up to 21 different strain types were identified (14d/g in 27.4%; 14f/g in 14.5%). Macrolide resistance mutations were present in 95% and tetracycline in 0%. Conclusion: Several different strains co-exist in Barcelona with a high proportion of macrolide resistance and absence of tetracycline resistance.

mcr-Colistin Resistance Genes Mobilized by IncX4, IncHI2, and IncI2 Plasmids in Escherichia coli of Pigs and White Stork in Spain.

Colistin has become the last-line antimicrobial for the treatment of multidrug resistant (MDR) Enterobacterales in human medicine. To date, several colistin resistance genes have been described. Of them mcr-1 is disseminated worldwide in Escherichia coli of human and animal origin. The aim of this study was to characterize mcr-mediated resistance plasmids from E. coli of animal origin in Spain. From our strain collection, 70 E. coli of pig origin collected between 2005 and 2014 (10 per year, except for years 2009-2010-2013) were randomly selected and screened for the presence of mcr-genes. Additionally, 20 E. coli isolated in 2011 from white storks (Ciconia ciconia) from the same urban household waste landfill associated colony were also included. Whole genome sequencing of mcr-positive isolates was carried out on a MiSeq (Illumina). Hybrid whole genome sequencing strategy combining nanopore and Illumina technologies were performed in a selection of isolates to close the genomes and plasmids and identify the presence of antimicrobial resistance genes. Minimum inhibitory concentration (MIC) was used to assess the susceptibility to colistin. Mating experiments were carried out to evaluate transferability of the mcr-genes. A total of 19 mcr-1 and one mcr-4 positive isolates were detected, 15 from pigs distributed during the study period, and five from storks collected in 2011. No other mcr-variants were found. The MICs for colistin ranged between 4 and >4 mg/L. High diversity of STs were detected among the mcr-1 positive E. coli isolates, with only ST-10 shared between pigs and white storks. Except for one isolate, all were genotypic and phenotypically MDR, and five of them also harbored cephalosporin resistance genes (bla CTX-M- 14, bla SHV- 12, and three bla CMY- 2). mcr-1 genes were mobilizable by conjugation, associated with IncX4, IncHI2, and IncI2 plasmids. In our study, mcr-1 genes have been circulating in pig farms since 2005 harbored by a variety of E. coli clones. Its persistence may be driven by co-selection since plasmids containing mcr-1 also exhibit resistance to multiple drugs used in veterinary medicine. Furthermore, this is the first report of the presence of mcr-1 gene in isolates from white storks in Spain. This finding highlights the potential importance of wildlife that forage at urban household waste landfills in the transmission and spread of colistin resistance genes.

Early Oral Switch to Linezolid for Low-risk Patients With Staphylococcus aureus Bloodstream Infections: A Propensity-matched Cohort Study.

BACKGROUND: Oral switch to linezolid is a promising alternative to standard parenteral therapy (SPT) in Staphylococcus aureus bacteremia (SAB). METHODS: We conducted a prospective cohort study of all adult cases of SAB between 2013 and 2017 in a Spanish university hospital. We compared the efficacy, safety, and length of hospital stay of patients receiving SPT and those where SPT was switched to oral linezolid between days 3 and 9 of treatment until completion. We excluded complicated SAB and osteoarticular infections. A k-nearest neighbor algorithm was used for propensity score matching with a 2:1 ratio. RESULTS: After propensity score matching, we included 45 patients from the linezolid group and 90 patients from the SPT group. Leading SAB sources were catheter related (49.6%), unknown origin (20.0%), and skin and soft tissue (17.0%). We observed no difference in 90-day relapse between the linezolid group and the SPT group (2.2% vs 4.4% respectively; P = .87). No statistically significant difference was observed in 30-day all-cause mortality between the linezolid group and the SPT group (2.2% vs 13.3%; P = .08). The median length of hospital stay after onset was 8 days in the linezolid group and 19 days in the SPT group (P < .01). No drug-related events leading to discontinuation were noted in the linezolid group. CONCLUSIONS: Treatment of SAB in selected low-risk patients with an oral switch to linezolid between days 3 and 9 of treatment until completion yielded similar clinical outcomes as SPT, allowing earlier discharge from the hospital.

Detection of Bacteriophage Particles Containing Antibiotic Resistance Genes in the Sputum of Cystic Fibrosis Patients.

Cystic fibrosis (CF) is a chronic disease in which the bacterial colonization of the lung is linked to an excessive inflammatory response that leads to respiratory failure. The microbiology of CF is complex. Staphylococcus aureus is the first bacterium to colonize the lungs in 30% of pediatric CF patients, and 80% of adult patients develop a chronic Pseudomonas aeruginosa infection, but other microorganisms can also be found. The use of antibiotics is essential to treat the disease, but antibiotic performance is compromised by resistance mechanisms. Among various mechanisms of transfer of antibiotic resistance genes (ARGs), the recently been reported bacteriophages are the least explored in clinical settings. To determine the role of phages in CF as mobile genetic elements (MGEs) carrying ARGs, we evaluated their presence in 71 CF patients. 71 sputum samples taken from these patients were screened for eight ARGs (blaTEM, blaCTX-M-1-group, blaCTX-M-9-group, blaOXA-48, blaVIM, mecA, qnrA, and qnrS) in the bacteriophage DNA fraction. The phages found were also purified and observed by electron microscopy. 32.4% of CF patients harbored ARGs in phage DNA. ß-lactamase genes, particularly blaVIM and blaTEM, were the most prevalent and abundant, whereas mecA, qnrA, and qnrS were very rare. Siphoviridae phage particles capable of infecting P. aeruginosa and Klebsiella pneumoniae were detected in CF sputum. Phage particles harboring ARGs were found to be abundant in the lungs of both CF patients and healthy individuals and could contribute to the colonization of multiresistant strains.

18F-FDG-PET/CT angiography in the diagnosis of infective endocarditis and cardiac device infection in adult patients with congenital heart disease and prosthetic material.

OBJECTIVES: Infective endocarditis (IE) and cardiac device infection (CDI) are a major complication in the growing number of patients with congenital heart disease (CHD) reaching adulthood. We aimed to evaluate the added value of 18F-FDG-PET/CT angiography (PET/CTA) in the diagnosis of IE-CDI in adults with CHD and intravascular or intracardiac prosthetic material, in whom echocardiography (ECHO) and modified Duke Criteria (DC) have limitations because of the patients' complex anatomy. METHODS: A prospective study was conducted in a referral center with multidisciplinary IE and CHD Units. PET/CTA and ECHO findings were compared in consecutive adult (≥18years) patients with CHD who have prosthetic material and suspected IE-CDI. The initial diagnosis using the DC and the diagnosis with the additional PET/CTA data (DC+PET/CTA) were compared with the final diagnostic consensus established by an expert team at three months. RESULTS: Between November-2012 and April-2017, 25 patients (15 men; median age 40years) were included. Cases were initially classified as definite in 8 (32%), possible in 14 (56%) and rejected in 3 (12%). DC+PET/CTA allowed reclassification of 12/14 (86%) cases initially identified as possible IE. The sensitivity, specificity, PPV, NPV, and accuracy of DC at IE suspicion were 39.1%/83.3%/90.4%/25.5%/61.2%, respectively. The diagnostic performance increased significantly with addition of PET/CTA data: 87%/83.3%/95.4%/61.5%/85.1%, respectively. PET/CTA also provided an alternative diagnosis in 3 patients with rejected IE, and detected pulmonary embolisms in 3 patients. CONCLUSIONS: PET/CTA was a useful diagnostic tool in the complex group of adult patients with CHD who have cardiac or intravascular prosthetic material and suspected IE or CDI, providing added diagnostic value to the modified DC (increased sensitivity) and improving case classification.

A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities.

Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.

Human multidrug-resistant Mycobacterium bovis infection in Mexico.

Here, we describe the molecular characterization of six human Mycobacterium bovis clinical isolates, including three multidrug resistant (MDR) strains, collected in Mexico through the National Survey on Tuberculosis Drug Resistance (ENTB-2008), a nationally representative survey conducted during 2008-2009 in nine states with a stratified cluster sampling design. The genetic background of bovine M. bovis strains identified in three different states of Mexico was studied in parallel to assess molecular relatedness of bovine and human strains. Additionally, resistance to first and second line anti-tuberculosis (TB) drugs and molecular identification of mutations conferring drug resistance was also performed. All strains were characterized by spoligotyping and 24-loci MIRU-VNTRs, and analyzed using the SITVIT2 (n = 112,000 strains) and SITVITBovis (n = 25,000 strains) proprietary databases of Institut Pasteur de la Guadeloupe. Furthermore, data from this study (n = 55 isolates), were also compared with genotypes recorded for M. bovis from USA (n = 203), Argentina (n = 726), as well as other isolates from Mexico (independent from the present study; n = 147), to determine any evidence for genetic relatedness between circulating M. bovis strains. The results showed that all human M. bovis cases were not genetically related between them or to any bovine strain. Interestingly, a high degree of genetic variability was observed among bovine strains. Several autochthonous and presumably imported strains were identified. The emergence of drug-resistant M. bovis is an important public health problem that jeopardizes the success of TB control programs in the region.

Effects of velocity-based resistance training on young soccer players of different ages.

This study aimed to analyze the effect of velocity-based resistance training (RT) with moderate loads and few repetitions per set combined with jumps and sprints on physical performance in young soccer players of different ages. A total of 44 elite youth soccer players belonging to 3 teams participated in this study: an under-16 team (U16, n = 17) and an under-18 team (U18, n = 16) performed maximal velocity RT program for 26 weeks in addition to typical soccer training, whereas an under-21 team (U21, n = 11) did not perform RT. Before and after the training program, all players performed 20-m running sprint (T20), countermovement jump (CMJ), a progressive isoinertial loading test in squat to determine the load that elicited a ∼ 1 m · s(-1) velocity (V1LOAD) and an incremental field test to determine maximal aerobic speed (MAS). U16 showed significantly (p = 0.000) greater gains in V1LOAD than U18 and U21 (100/0/0%). Only U16 showed significantly (p = 0.01) greater gains than U21 (99/1/0%) in CMJ height. U18 obtained a likely better effect on CMJ performance than U21 (89/10/1%). The beneficial effects on T20 between groups were unclear. U16 showed a likely better effect on MAS than U21 (80/17/3%), whereas the rest of comparisons were unclear. The changes in CMJ correlated with the changes in T20 (r = -0.49) and V1LOAD (r = 0.40). In conclusion, velocity-based RT with moderate load and few repetitions per set seems to be an adequate method to improve physical performance in young soccer players.

Estudio comparativo de dos programas de entrenamiento de la memoria en personas mayores con quejas subjetivas de memoria: un análisis preliminar / Differential effectiveness for two memory training programs in older adults with subjective memory complaints (mnemonic training vs. everyday forgetfulness training): an exploratory analysis

Introducción: A pesar del declive cognitivo que se produce con la edad, numerosos estudios han demostrado la eficacia que tienen los programas de entrenamiento de la memoria para mejorar diversas áreas neurocognitivas en las personas mayores. Objetivo: analizar de forma preliminar el efecto diferencial de dos programas de entrenamiento de la memoria en personas mayores sobre diversas funciones cognitivas. Método: 18 sujetos entre 61 y 81 años han participado, o bien en un programa de entrenamiento en estrategias de memoria, o bien en un programa de entrenamiento en olvidos cotidianos. En todos ellos se evaluó la percepción subjetiva de la memoria, así como el desempeño cognitivo antes y después del entrena-miento. Resultados: se encontró una mejoría estadísticamente significativa en el cuestionario de quejas subjetivas de memoria en ambos grupos, y sólo se encontró cierta mejoría en memoria de trabajo visoespacial (test Corsi inverso) y en razonamiento (Analogías) en el grupo que recibió un entrena-miento en olvidos cotidianos. Conclusiones: los programas de entrenamiento de la memoria mejoran la percepción subjetiva que tienen las personas mayores del funcionamiento de la memoria, y ello es independiente de la metodología de entrenamiento utilizada

Introduction: Despite the cognitive decline that occurs with age, several studies have showed the effectiveness of memory training programs for improving some neurocognitive functions in older people. Objective: to analyze in a preliminary way the differential effect of two memory training programs on several areas of cognition in older adults. Method: 18 older adults between 61 and 81 years have participated, either in a memory strategies training program, either an everyday forgetfulness training program. All of them evaluated the subjective perception of memory and cognitive performance before and after training. Results: A statistically significant improvement in the questionnaire of subjective memory complaints was found in both groups, and only the group receiving everyday forgetfulness training improved in some cognitive performances in visuospatial working memory (Corsi test reverse) and reasoning (analogies). Conclusions: Memory training programs improve the subjective perception that older people have about its functioning, and this is independent of training methodology used

Alteraciones psicológicas en menores expuestos a violencia de género: Prevalencia y diferencias de género y edad / Psychological disorders in children exposed to intimate partner violence: prevalence and gender and age differences

Antecedentes: La exposición de menores a la violencia del padre hacía la madre es un tipo de maltrato infantil y conlleva consecuencias psicológicas muy negativas. Este trabajo expone las características y prevalencias de ocho síndromes empíricos en menores expuestos. Método: Un total de 91 menores expuestos a violencia de género fueron valorados a través del Child Behavior Checklist (CBCL) en un programa de Intervención Psicológica. Se analizan los resultados y prevalencias de ocho síndromes empíricos de la muestra total, por sexo y por edad en comparación con población normal. Resultados: Los menores expuestos a violencia de género remitidos a consulta clínica, difieren significativamente de la población normal. La prevalencia clínica de los síndromes es significativamente superior con respecto a lo esperable en menores de su edad (hasta 10 veces superior). Las niñas y los menores de menor edad suelen manifestar prevalencias superiores. Conclusiones: La exposición a violencia de género determina en los/as menores graves consecuencias psicológicas que influyen negativamente en su bienestar, desarrollo psicológico y salud mental y que hacen necesario atender este importante problema social (AU)

Background: Children’s exposure to intimate partner violence against women it is a kind of child maltreatment and it carries very negative psychological consequences. This work shows the prevalences and characteristics of eight empirical syndromes in exposed children. Method: A number of 91 exposed children to intimate partner violence were assessed through the Child Behavior Checklist (CBCL) in a Psychological Intervention Program. The results are analyzed and eight empirical syndromes prevalences total sample, by gender and age compared to normal population. Results: The children exposed to intimate partner violence show higher prevalence in all syndromes than normal population. The clinical prevalence of syndromes can become 10 times higher than normal population. Moreover, girls and younger children show higher prevalences. Conclusions: Children's exposure to intimate partner violence can cause important psychological consequences what impacts in welfare, mental health and how the child develops psychologically. Therefore, it's necessary to address this important social problem (AU)

Un sistema de clasificación de los diseños de investigación en psicología / A classification system for research designs in psychology

En este trabajo se elabora un marco conceptual y se desarrollan unos principios básicos para fundamentar un sistema de clasificación de los diseños de investigación más usuales en psicología basado en tres estrategias (manipulativa, asociativa y descriptiva) de donde emanan varios tipos de estudios, tres para la estrategia manipulativa (experimentales, cuasiexperimentales y de caso único), tres para la asociativa (comparativos, predictivos y explicativos) y dos para la descriptiva (observacionales y selectivos) (AU)

In this work we devise a conceptual framework and develop some basic principles to promove a classification system for the most usual research designs in psychology based on three strategies (manipulative, associative and descriptive) from which emerge different types of studies, three for manipulative strategy (experimental, quasi-experimental and single-case), three for associative strategy (comparative, predictive and explanatory) and two for descriptive strategy (observational and selective) (AU)

Expression and activation of intracellular receptors TLR7, TLR8 and TLR9 in peripheral blood monocytes from HIV-infected patients / Expresión y activación de receptores intracelulares TLR7, TLR8 y TLR9 en monocitos de sangre periférica de pacientes infectados con VIH

Introduction: TLR´s play a role in host defense in HIV infection recognizing the viral DNA or RNA. Their activation induces a signaling pathway that includes the proteins MyD88, IRAK4, TRAF6 and the transcription factor NF-kBp65. Objective: To determine the expression of TLR7, TLR8 and TLR9, and activation of its signaling pathway in monocytes from patients infected with HIV. Methods. Expression of TLR7, TLR8 and TLR9 was determined in monocytes from HIV-infected patients (n= 13) and control subjects (n= 13), which were activated with specific ligands. The expression of MyD88 and NF-kBp65 were determined by flow cytometry; IRAK4 and TRAF6 were studied by immunoblotting. Results: No statistical difference was found in the expression of TLR7, 8 and 9 in monocytes from patients compared to controls, but we observed the non-significant increased expression of TLR9 in patients. The activation showed no significant difference in the expression of MyD88 and NF-kBp65 in patients when compared to controls, but were decreased in stimulated cells over non-stimulated cells. IRAK4 and TRAF6 were not detected. Conclusions: No statistical difference was observed in the expression of intracellular TLRs, MyD88 and NFkBp65 in monocytes from patients compared to controls. This was probably due to effective antiretroviral therapy being received at the time of study entry. Additional studies are needed under controlled conditions that include infected patients with and without ARVT, responders and non-responders, and work with different cell populations.

Introducción: En la infección por VIH los TLR juega un papel en la defensa del huésped al reconocer el ADN o ARN viral. Su activación induce la vía de señalización que incluye las proteínas MyD88, IRAK4, TRAF6 y el factor de transcripción NF-kBp65. Objetivo: Determinar la expresión del TLR7, TLR8 y TLR9, y activación de su vía de señalización en monocitos de pacientes infectados con VIH. Métodos: Se determinó la expresión de TLR7, TLR8 y TLR9 en monocitos de pacientes infectados con VIH (n =13) y sujetos control (n =13), se activaron con ligandos específicos y se determinó la expresión de MyD88 y NF-kBp65 por citometría de flujo. IRAK4 y TRAF6 fueron estudiadas por inmunoelectrotransferencia. Resultados: No se observó diferencia estadística en la expresión de TLR7, 8 y 9 en los monocitos de pacientes con respecto a los controles, pero observamos aumento no significante del TLR9 en los pacientes. La activación no mostró diferencia significativa en la expresión de MyD88 y NF-kBp65 en pacientes con respecto a los controles, pero se encontraron disminuidas en células estimuladas con respecto a las no estimuladas. IRAK4 y TRAF6 no se detectaron. Conclusiones: No se observó diferencia en la expresión de los TLR, ni en la expresión de MyD88 y NFkBp65, en monocitos de pacientes con respecto a los controles probablemente debido a la terapia antirretroviral recibida al momento del estudio. Se sugieren estudios con pacientes con y sin TARV, respondedores y no respondedores, y trabajar con diferentes poblaciones celulares.

Expression and activation of intracellular receptors TLR7, TLR8 and TLR9 in peripheral blood monocytes from HIV-infected patients.

INTRODUCTION: TLR´s play a role in host defense in HIV infection recognizing the viral DNA or RNA. Their activation induces a signaling pathway that includes the proteins MyD88, IRAK4, TRAF6 and the transcription factor NF-kBp65. OBJECTIVE: To determine the expression of TLR7, TLR8 and TLR9, and activation of its signaling pathway in monocytes from patients infected with HIV. Methods. Expression of TLR7, TLR8 and TLR9 was determined in monocytes from HIV-infected patients (n= 13) and control subjects (n= 13), which were activated with specific ligands. The expression of MyD88 and NF-kBp65 were determined by flow cytometry; IRAK4 and TRAF6 were studied by immunoblotting. RESULTS: No statistical difference was found in the expression of TLR7, 8 and 9 in monocytes from patients compared to controls, but we observed the non-significant increased expression of TLR9 in patients. The activation showed no significant difference in the expression of MyD88 and NF-kBp65 in patients when compared to controls, but were decreased in stimulated cells over non-stimulated cells. IRAK4 and TRAF6 were not detected. CONCLUSIONS: No statistical difference was observed in the expression of intracellular TLRs, MyD88 and NFkBp65 in monocytes from patients compared to controls. This was probably due to effective antiretroviral therapy being received at the time of study entry. Additional studies are needed under controlled conditions that include infected patients with and without ARVT, responders and non-responders, and work with different cell populations.

INTRODUCCIÓN: En la infección por VIH los TLR juega un papel en la defensa del huésped al reconocer el ADN o ARN viral. Su activación induce la vía de señalización que incluye las proteínas MyD88, IRAK4, TRAF6 y el factor de transcripción NF-kBp65. OBJETIVO: Determinar la expresión del TLR7, TLR8 y TLR9, y activación de su vía de señalización en monocitos de pacientes infectados con VIH. MÉTODOS: Se determinó la expresión de TLR7, TLR8 y TLR9 en monocitos de pacientes infectados con VIH (n= 13) y sujetos control (n= 13), se activaron con ligandos específicos y se determinó la expresión de MyD88 y NF-kBp65 por citometría de flujo. IRAK4 y TRAF6 fueron estudiadas por inmunoelectrotransferencia. RESULTADOS: No se observó diferencia estadística en la expresión de TLR7, 8 y 9 en los monocitos de pacientes con respecto a los controles, pero observamos aumento no significante del TLR9 en los pacientes. La activación no mostró diferencia significativa en la expresión de MyD88 y NF-kBp65 en pacientes con respecto a los controles, pero se encontraron disminuidas en células estimuladas con respecto a las no estimuladas. IRAK4 y TRAF6 no se detectaron. CONCLUSIONES: No se observó diferencia en la expresión de los TLR, ni en la expresión de MyD88 y NFkBp65, en monocitos de pacientes con respecto a los controles probablemente debido a la terapia antirretroviral recibida al momento del estudio. Se sugieren estudios con pacientes con y sin TARV, respondedores y no respondedores, y trabajar con diferentes poblaciones celulares.