Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms.

AIM: The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB). MATERIALS/METHODS: The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. RESULTS/CONCLUSIONS: After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.

Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

El síndrome de Terson diagnosticado por ecografía como indicador de extrema gravedad en pacientes neurocríticos / Ultrasound diagnosis of Terson syndrome as an indicator of extreme severity in neurocritical care patients

Introducción: Se denomina síndrome de Terson (ST) a cualquier tipo de hemorragia intraocular (HIO), identificada en pacientes con patología aguda intracraneal. El ST parece estar relacionado con la gravedad clínica en la hemorragia subaracnoidea (HSA), pero en pacientes con trauma craneoencefálico (TCE) y hemorragia intracerebral (HIC), su asociación está por definir. Diseñamos este estudio para evaluar el rendimiento de la ecografía ocular (EO) y su utilidad en la práctica clínica.Materiales y métodosRealizamos un estudio observacional prospectivo, unicéntrico en pacientes neurocríticos. Analizamos los casos con respecto a los controles, identificados con oftalmoscopia indirecta (OI), y por EO. Determinamos las características diagnósticas de la EO. Hicimos un análisis multivariante para determinar asociaciones clínicamente relevantes.ResultadosSe incluyeron 91 pacientes con diagnósticos de HIC (41,76%), HSA (29,67%) y TCE (28,57%). El ST fue identificado por EO en ocho pacientes (8,79%) y en 24 pacientes (24,37%) por OI. La mortalidad ajustada para los pacientes con ST tuvo una OR 4,15 con IC 95% (1,52 - 11,33). Todos los pacientes con ST identificados por EO presentaron una escala de coma de Glasgow < 9 y tuvieron un riesgo elevado de precisar craniectomía descompresiva, una OR 9,84 (1,64 - 59). La EO alcanzó una sensibilidad global de 30,43%, una especificidad del 98,53%, con una precisión diagnóstica de 81,32. Para la detección de la hemorragia vítrea, una sensibilidad y especificidad del 87,5 y 98,5%, respectivamente.ConclusionesEl ST diagnosticado por EO discrimina pacientes neurocríticos de extrema gravedad que pueden requerir el máximo escalón terapéutico y es un factor independiente de mortalidad intrahospitalaria. (AU)

Introduction: Terson syndrome (TS) is defined as any intraocular haemorrhage identified in patients with acute intracranial pathology. TS appears to be associated with clinical severity in patients with subarachnoid haemorrhage (SAH), but the association is yet to be defined in patients with traumatic brain injury (TBI) and intracerebral haemorrhage (ICH). This study aimed to evaluate the diagnostic performance of ocular ultrasound (OU) and its usefulness in clinical practice.Material and methodsWe performed an observational, prospective, single-centre study of neurocritical care patients. We analysed cases and controls, defined according to indirect ophthalmoscopy (IO) and OU findings. We determined the diagnostic characteristics of OU. A multivariate analysis was performed to identify clinically relevant associations.ResultsThe sample included 91 patients diagnosed with ICH (41.76%), SAH (29.67%), and TBI (28.57%). TS was identified by OU in 8 patients (8.79%) and by IO in 24 (24.37%). The adjusted mortality rate in patients with TS showed an odds ratio (OR) of 4.15 (95% confidence interval [CI], 1.52-11.33). All patients with TS detected by OU presented Glasgow Coma Scale scores < 9, with an elevated risk of needing decompressive craniectomy (OR: 9.84; 95% CI, 1.64-59). OU presented an overall sensitivity of 30.43%, specificity of 98.53%, and diagnostic accuracy of 81.32%. For the detection of vitreous haemorrhage, sensitivity and specificity were 87.5% and 98.5%, respectively.ConclusionsOU diagnosis of TS identifies extremely critical patients, who may require the highest level of care; TS is an independent risk factor for in-hospital mortality. (AU)

CD8+ lymphocytes do not impact SIV reservoir establishment under ART.

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8+ T cells are important during the initial control of viral replication. Here we examined the effect of CD8+ T cells on formation of the latent reservoir in simian immunodeficiency virus (SIV)-infected macaques by performing experimental CD8+ depletion either before infection or before early (that is, day 14 post-infection) ART initiation. We found that CD8+ depletion resulted in slower decline of viremia, indicating that CD8+ lymphocytes reduce the average lifespan of productively infected cells during acute infection and early ART, presumably through SIV-specific cytotoxic T lymphocyte (CTL) activity. However, CD8+ depletion did not change the frequency of infected CD4+ T cells in the blood or lymph node as measured by the total cell-associated viral DNA or intact provirus DNA assay. In addition, the size of the persistent reservoir remained the same when measuring the kinetics of virus rebound after ART interruption. These data indicate that during early SIV infection, the viral reservoir that persists under ART is established largely independent of CTL control.

Ultrasound diagnosis of Terson syndrome as an indicator of extreme severity in neurocritical care patients.

INTRODUCTION: Terson syndrome (TS) is defined as any intraocular haemorrhage identified in patients with acute intracranial pathology. TS appears to be associated with clinical severity in patients with subarachnoid haemorrhage (SAH), but the association is yet to be defined in patients with traumatic brain injury (TBI) and intracerebral haemorrhage (ICH). This study aimed to evaluate the diagnostic performance of ocular ultrasound (OU) and its usefulness in clinical practice. MATERIAL AND METHODS: We performed an observational, prospective, single-centre study of neurocritical care patients. We analysed cases and controls, defined according to indirect ophthalmoscopy (IO) and OU findings. We determined the diagnostic characteristics of OU. A multivariate analysis was performed to identify clinically relevant associations. RESULTS: The sample included 91 patients diagnosed with ICH (41.76%), SAH (29.67%), and TBI (28.57%). TS was identified by OU in 8 patients (8.79%) and by IO in 24 (24.37%). The adjusted mortality rate in patients with TS showed an odds ratio (OR) of 4.15 (95% confidence interval [CI], 1.52-11.33). All patients with TS detected by OU presented Glasgow Coma Scale scores < 9, with an elevated risk of needing decompressive craniectomy (OR: 9.84; 95% CI, 1.64-59). OU presented an overall sensitivity of 30.43%, specificity of 98.53%, and diagnostic accuracy of 81.32%. For the detection of vitreous haemorrhage, sensitivity and specificity were 87.5% and 98.5%, respectively. CONCLUSIONS: OU diagnosis of TS identifies extremely critical patients, who may require the highest level of care; TS is an independent risk factor for in-hospital mortality.

Density assessment and reporting for Phlebotomus perniciosus and other sand fly species in periurban residential estates in Spain.

Green periurban residential areas in Mediterranean countries have flourished in the last decades and become foci for leishmaniasis. To remedy the absence of information on vector ecology in these environments, we examined phlebotomine sand fly distribution in 29 sites in Murcia City over a 3-year period, including the plots of 20 detached houses and nine non-urbanized sites nearby. We collected 5,066 specimens from five species using "sticky" interception and light attraction traps. The relative frequency of the main Leishmania infantum vector Phlebotomus perniciosus in these traps was 32% and 63%, respectively. Sand fly density was widely variable spatially and temporally and greatest in non-urbanized sites, particularly in caves and abandoned buildings close to domestic animal holdings. Phlebotomus perniciosus density in house plots was positively correlated with those in non-urbanized sites, greatest in larger properties with extensive vegetation and non-permanently lived, but not associated to dog presence or a history of canine leishmaniasis. Within house plots, sand fly density was highest in traps closest to walls. Furthermore, the study provides a guideline for insect density assessment and reporting and is envisioned as a building block towards the development of a pan-European database for robust investigation of environmental determinants of sand fly distribution.

Significance of a polymerase chain reaction method in the detection of Clostridioides difficile.

OBJECTIVE: Clostridioides difficile (CD) is the most common cause of nosocomial diarrhea. Detection of CD toxin in patients' faecal samples is the traditional rapid method for the diagnosis of CD infection. Various testing algorithms have been proposed: an initial screening test using a rapid test, and a confirmatory test (cytotoxicity neutralization assay, toxigenic culture, nucleic acid amplification test) for discordant results. The aim of this study was to evaluate the effectiveness of a two-step algorithm using an immunochromatographic test followed of a polymerase chain reaction (PCR). METHODS: The specimens have been tested according to the following schedule: 1) Step one: All samples were tested for detection of glutamate dehydrogenase antigen (GDH) and toxin A/B using the C. diff QUIK CHEK Complete test. All GDH and toxins positive results were considered CD positives; 2) Step two: When the results were discrepant (only GDH+ or toxins+), the samples were confirmed using the PCR test BD MAX Cdiff. All PCR positive results were considered CD positives. RESULTS: A total of 2,138 specimens were initially tested. 139 were positive for GDH and toxins. 160 discrepant results (148 GDH+ and 12 toxins+) were tested by PCR, 117 were positive (107/148 GDH+ and 10/12 toxins+). CONCLUSIONS: The implementation of a PCR method showed an increase de 117 positive results (73.1% of discrepant). Considering the sensitivity of C.diff QUIK CHEK (instructions of manufacturer), the GDH discrepant results may be false negatives, y the samples PCR and toxins positives may be real positives results.

Analysis of penitentiary, social and legal operators' perceptions of prison inmates with intellectual disabilities.

OBJECTIVE: To analyze the different perceptions of professionals about the problem of intellectual disability in the prison setting. MATERIAL AND METHOD: Exploratory-descriptive type. In-depth interviews with legal, social and prison operators of Centro Penitenciario de Zuera (Zaragoza). RESULTS: The narratives of the interviewed subjects point to the aggravating circumstances that a closed social environment can entail for inmates with intellectual disabilities. Communications in the prison administration are written in a technical language that is not understandable for inmates with intellectual deficits. DISCUSION: There is a need to give more visibility to the case of inmates with intellectual disabilities. Procedures also need to be applied that favour greater cognitive accessibility for this profile of inmates, along with the promotion of awareness raising and training for professionals to enable them to deal with this issue.

Ultrasound diagnosis of Terson syndrome as an indicator of extreme severity in neurocritical care patients. / El síndrome de Terson diagnosticado por ecografía como indicador de extrema gravedad en pacientes neurocríticos.

INTRODUCTION: Terson syndrome (TS) is defined as any intraocular haemorrhage identified in patients with acute intracranial pathology. TS appears to be associated with clinical severity in patients with subarachnoid haemorrhage (SAH), but the association is yet to be defined in patients with traumatic brain injury (TBI) and intracerebral haemorrhage (ICH). This study aimed to evaluate the diagnostic performance of ocular ultrasound (OU) and its usefulness in clinical practice. MATERIAL AND METHODS: We performed an observational, prospective, single-centre study of neurocritical care patients. We analysed cases and controls, defined according to indirect ophthalmoscopy (IO) and OU findings. We determined the diagnostic characteristics of OU. A multivariate analysis was performed to identify clinically relevant associations. RESULTS: The sample included 91 patients diagnosed with ICH (41.76%), SAH (29.67%), and TBI (28.57%). TS was identified by OU in 8 patients (8.79%) and by IO in 24 (24.37%). The adjusted mortality rate in patients with TS showed an odds ratio (OR) of 4.15 (95% confidence interval [CI], 1.52-11.33). All patients with TS detected by OU presented Glasgow Coma Scale scores < 9, with an elevated risk of needing decompressive craniectomy (OR: 9.84; 95% CI, 1.64-59). OU presented an overall sensitivity of 30.43%, specificity of 98.53%, and diagnostic accuracy of 81.32%. For the detection of vitreous haemorrhage, sensitivity and specificity were 87.5% and 98.5%, respectively. CONCLUSIONS: OU diagnosis of TS identifies extremely critical patients, who may require the highest level of care; TS is an independent risk factor for in-hospital mortality.

Salivary D-dimer in pigs: Validation of an automated assay and changes after acute stress.

D-dimer is a peptide found in serum and is derived from the degradation of blood clots. Even though it has been analysed in human saliva, D-dimer has not been previously evaluated in the saliva of any veterinary species, and its source and role remain unknown. The objectives of this research were firstly, to validate the use of an automated method for the measurement of D-dimer in porcine saliva, and secondly, to evaluate whether D-dimer concentration changes in pig saliva after an acute stress stimulus. For this purpose, a complete analytical validation of a commercially-available immunoturbidimetric assay was carried out. In addition, an experimental acute stress model was induced in 11 pigs based on a technique involving restraint by nose-snare immobilisation for 1 min. Saliva samples were subsequently collected at different times and D-dimer, salivary alpha-amylase (sAA) and cortisol were assessed in order to evaluate changes in its concentrations after the stress induction. The D-dimer automated assay showed adequate reproducibility and sensitivity, with coefficients of variation below 10% and a limit of quantification of 0.167 µg/mL fibrinogen equivalent units (FEU). It also showed a high accuracy, determined by linearity under dilution and recovery tests. In the stress model, a significant increase (P < 0.05) in salivary D-dimer 15 min after the stress stimulus and a positive correlation between D-dimer and sAA (r = 0.51; P < 0.001) were observed. These results indicate that D-dimer can be measured in porcine saliva with an automated method and suggest that its concentration can be influenced by stressful conditions.

Reaction strategies for the enzymatic synthesis of neopentyl glycol diheptanoate.

This work describes for the first time the green synthesis of neopentyl glycol diheptanoate in a solvent-free medium via an enzymatic pathway. The process has been carried out in an open-air reactor in order to ease water removal through evaporation and shift the chemical equilibrium towards product formation. The inhibiting effect of high concentrations of heptanoic acid has been put into evidence by a reduction of initial reaction rate when esterification was performed with stoichiometric amounts of substrates. Therefore, in this work different strategies for the stepwise addition of heptanoic acid are proposed, and best results were obtained when stoichiometric quantities of acid were divided in four equal amounts and added when previous batch was consumed. Biocatalyst Novozym® 435 concentration and temperature were optimised, giving yields of 90% in neopentyl glycol diheptanoate when 7.5% (w/w) and 70 °C were used. With a remaining 7% of heptanoic acid (probably caused by the alcohol evaporation) the addition of neopentyl glycol led to a conversion of 95%. Thus, product can be used in cosmetics without further purification and can be labelled as environmentally-friendly synthesized because of its enzymatic origin.

Surfactant-templated zeolites for the production of active pharmaceutical intermediates.

A hierarchical USY zeolite has been produced using the surfactant-templating method and used as a catalyst for the production of two important active pharmaceutical ingredients. The presence of intracrystalline mesoporosity in the zeolite results in a significant increase in both the activity (up to 30 fold increase in TOF) and reusability for Friedel-Crafts alkylation and aldol condensation steps.

[Colonization rates by Streptococcus agalactiae in Spanish and foreign pregnant women in the Fuenlabrada University Hospital]. / Tasas de colonización por Streptococcus agalactiae en gestantes españolas y extranjeras en el Hospital Universitario de Fuenlabrada.

OBJECTIVE: In pregnant women, the rectovaginal colonization by Streptococcus agalactiae (GBS) is related with geographic area of origin (6.5% to 36%). It was analysed GBS carriage in pregnant women in 2012-2014 in our hospital. METHODS: Observational retrospective study about GBS isolates from rectovaginal samples (RVS) and urine cultures of Spanish and immigrant pregnant women in 2012-2014. It was considered only a single isolation for patient. There were excluded women with GBS in urine samples of RVS study. RESULTS: A total of 4,648 Spanish and 1,405 immigrant women were analysed. GBS was detected in urine samples in 231 Spanish (5%) and 106 immigrant (7.6%). A total of 5,716 RVS were analysed, GBS was detected in 10.5% of Spanish women and in 18.9% of immigrant women. CONCLUSIONS: The overall colonization in immigrant women is higher than in Spanish with the exception of Asian women. Cases of GBS detected in urine samples might serve as a possible explanation for the high rate of GBS carriage.

Attachment security, values, and prosocial attitudes.

The objective of this study was to determine whether individuals with different attachment styles held different prosocial values and attitudes given their different models of self and of others. A sample of 717 university students completed the ECR-S (Experiences in Close Relationships-Spanish) and the PVQ (Portrait Values Questionnaire), and evaluated different prosocial attitudes. The results showed that secure individuals reported higher scores on self-transcendence and in the value self-directions of the dimension openness to change, whereas insecure individuals had higher scores on conservation and self-enhancement. No differences were found in the attitudes of individuals with different attachment styles. These findings show a link between the dimensions of the universal values theory, and the models of self and of others.

Creation of Dystrophin Expressing Chimeric Cells of Myoblast Origin as a Novel Stem Cell Based Therapy for Duchenne Muscular Dystrophy.

Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression. This proof of concept study tested feasibility of myoblast fusion for Dystrophin Expressing. Chimeric Cell (DEC) therapy through in vitro characterization and in vivo assessment of engraftment, survival, and efficacy in the mdx mouse model of DMD. Murine DEC were created via ex vivo fusion of normal (snj) and dystrophin-deficient (mdx) myoblasts using polyethylene glycol. Efficacy of myoblast fusion was confirmed by flow cytometry and dystrophin immunostaining, while proliferative and myogenic differentiation capacity of DEC were assessed in vitro. Therapeutic effect after DEC transplant (0.5 × 106) into the gastrocnemius muscle (GM) of mdx mice was assessed by muscle functional tests. At 30 days post-transplant dystrophin expression in GM of injected mdx mice increased to 37.27 ± 12.1% and correlated with improvement of muscle strength and function. Our study confirmed feasibility and efficacy of DEC therapy and represents a novel SC based approach for treatment of muscular dystrophies.