New magnetic chelating sorbent for chromium speciation by magnetic solid phase extraction on-line with inductively coupled plasma optical emission spectrometry.

A novel sorbent material employing magnetic nanoparticles (MNPs) coupled to graphene oxide (GO) functionalized with 4-aminobenzenesulfonic acid (M@GO-ABS) has been synthesized and applied to develop an inexpensive and automatic method for Cr(III) and Cr(VI) speciation in environmental samples; the developed method combines inductively coupled plasma optical emission spectrometry (ICP-OES) with on-line magnetic solid phase extraction (MSPE). Two magnetic-knotted reactors containing M@GO-ABS were installed in the eight-port injection valve of a flow injection (FI) manifold. Two different eluents were used, one for Cr(VI) (the most toxic chromium species) and one for total Cr concentration. Cr(III) concentration was calculated by the difference between Cr(VI) concentration and total Cr concentration. The optimized method presented detection limits (LOD, peak height) of 0.1 µg L-1 for chromium (VI) and 0.08 µg L-1 for total chromium, and enrichment factors of 15 and 23, respectively. Certified reference materials (TMDA 54.5 fortified lake water and SPS-SW2 surface water) and spiked aqueous samples were used to validate the developed method. The developed method was fruitfully applied to chromium speciation in environmental water samples such as seawater, well water and tap water collected in Málaga (Spain). The obtained values were in good agreement with the certified values, and the recoveries were found in the range of 91-108% for the spiked samples.

Semiautomatic method for the ultra-trace arsenic speciation in environmental and biological samples via magnetic solid phase extraction prior to HPLC-ICP-MS determination.

A novel magnetic functionalized material based on graphene oxide and magnetic nanoparticles (MGO) was used to develop a magnetic solid phase extraction method (MSPE) to enrich both, inorganic and organic arsenic species in environmental waters and biological samples. An automatic flow injection (FI) system was used to preconcentrate the arsenic species simultaneously, while the ultra-trace separation and determination of arsenobetaine (AsBet), cacodylate, AsIII and AsV species were achieved by high performance liquid chromatography combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The sample was introduced in the FI system where the MSPE was performed, then 1 mL of eluent was collected in a chromatographic vial, which was introduced in the autosampler of HPLC-ICP-MS. Therefore, preconcentration and separation/determination processes were automatic and conducted separately. To the best of our knowledge, this is the first method combining an automatic MSPE with HPLC-ICP-MS for arsenic speciation, using a magnetic nanomaterial based on MGO for automatic MSPE. Under the optimized conditions, the LODs for the arsenic species were 3.8 ng L-1 AsBet, 0.5 ng L-1 cacodylate, 1.1 ng L-1 AsIII and 0.2 ng L-1 AsV with RSDs <5%. The developed method was validated by analyzing Certified Reference Materials for total As concentration (fortified lake water TMDA 64.3 and seawater CASS-6 NRC) and also by recovery analysis of the arsenic species in urine, well-water and seawater samples collected in Málaga. The developed method has shown promise for routine monitoring of arsenic species in environmental waters and biological fluids.

Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer's disease.

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that are highly relevant as disease biomarkers. Several studies that explored the role of miRNAs in Alzheimer's disease (AD) demonstrated their usefulness in clinical identification. Nevertheless, miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in AD. The objective of the study was to identify miRNAs that can be used as ECs in AD. METHODS: We evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini-Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aß42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 subjects without AD or any kind of dementia and negative for all core CSF biomarkers of AD, 25 subjects with MCI and negative for CSF biomarkers (MCI -), 22 subjects with MCI and positive for CSF biomarkers (MCI +), and 55 subjects with AD and positive for CSF biomarkers. In the discovery cohort, a profile of 384 miRNAs was determined in the plasma by TaqMan low-density array. The best EC candidates were identified by mean-centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper, and NormFinder algorithms. RESULTS: Nine miRNAs (hsa-miR-324-5p, hsa-miR-22-5p, hsa-miR-103a-2-5p, hsa-miR-362-5p, hsa-miR-425-3p, hsa-miR-423-5p, hsa-let-7i-3p, hsa-miR-532-5p, and hsa-miR-1301-3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa-miR-103a-2-5p was the best EC, followed by hsa-miR-22-5p, hsa-miR-1301-3p, and hsa-miR-425-3p, which had similar stability values in all three algorithms. CONCLUSIONS: We identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment.

Circulating MicroRNA Profile Associated with Obstructive Sleep Apnea in Alzheimer's Disease.

The diagnosis of obstructive sleep apnea (OSA) in Alzheimer's disease (AD) by polysomnography (PSG) is challenging due to the required collaboration of the patients. In addition, screening questionnaires have demonstrated limited usefulness with this subpopulation. Considering this, we investigated the circulating microRNA (miRNA) profile associated with OSA in AD patients. This study included a carefully selected cohort of females with mild-moderate AD confirmed by biological evaluation (n = 29). The individuals were submitted to one-night PSG to diagnose OSA (apnea-hypopnea index ≥ 15/h) and the blood was collected in the following morning. The plasma miRNA profile was evaluated using RT-qPCR. The patients had a mean (SD) age of 75.8 (5.99) years old with a body mass index of 28.6 (3.83) kg m-2. We observed a subset of 15 miRNAs differentially expressed between OSA and non-OSA patients, of which 10 were significantly correlated with the severity of OSA. Based on this, we built a prediction model that generated an AUC (95% CI) of 0.95 (0.88-1.00) including 5 of the differentially expressed miRNAs that correlated with OSA severity: miR-26a-5p, miR-30a-3p, miR-374a-5p, miR-377-3p, and miR-545-3p. Our preliminary results suggest a plasma miRNA signature associated with the presence of OSA in AD patients. Further studies will be necessary to validate these findings.

Neuropsychiatric symptoms and quality of life in Spanish patients with Alzheimer's disease during the COVID-19 lockdown.

BACKGROUND AND PURPOSE: The COVID-19 epidemic is affecting almost all individuals worldwide, and patients with Alzheimer's disease (AD) and amnesic mild cognitive impairment (MCI) are particularly at risk due to their characteristics and age. We analysed the impact of the pandemic on these patients' neuropsychiatric symptoms and their quality of life after 5 weeks of lockdown in Spain. METHODS: A total of 40 patients with a diagnosis of MCI (n = 20) or mild AD (n = 20) from the Cognitive Stimulation Program of the Cognitive Disorders Unit were evaluated. All patients had undergone a previous evaluation during the month before the lockdown, and were re-evaluated after 5 weeks of lockdown. The Neuropsychiatric Inventory (NPI) and EuroQol-5D questionnaire (EQ-5D) were used to assess neuropsychiatric symptoms in patients and the quality of life in patients as well in caregivers. RESULTS: The mean (SD) total baseline NPI score was 33.75 (22.28), compared with 39.05 (27.96) after confinement (P = 0.028). The most frequently affected neuropsychiatric symptoms were apathy [4.15 (3.78) vs. 5.75 (4.02); P = 0.002] and anxiety [3.95 (3.73) vs. 5.30 (4.01); P = 0.006] in patients with MCI, and apathy [2.35 (2.70) vs. 3.75 (3.78); P = 0.036], agitation [0.45 (1.14) vs. 1.50 (2.66); P = 0.029] and aberrant motor behaviour [1.25 (2.86) vs. 2.00 (2.93); P = 0.044] in patients with AD. We did not observe differences in EQ-5D scores during the re-evaluation. The 30% of patients and 40% of caregivers reported a worsening of the patients' health status during confinement. CONCLUSIONS: The results of this study show the worsening of neuropsychiatric symptoms in patients with AD and MCI during 5 weeks of lockdown, with agitation, apathy and aberrant motor activity being the most affected symptoms.

Cognitive-motor interference during gait in patients with Multiple Sclerosis: a mixed methods Systematic Review.

BACKGROUND: Cognitive-motor interference (CMI) has been proposed as a valid marker of daily life impairment in Multiple Sclerosis (MS). The heterogeneity and scarce number of studies regarding CMI in MS has hampered the synthesis of the existing evidence. The present systematic review employed a mixed methods approach with the aim of identifying and describing variables under which CMI is particularly useful to assess patients with MS. RESULTS: MS patients showed significant CMI. The motor variables that were most sensitive in detecting significant CMI were velocity (m/s), cadence (steps/min), and double support (% gait cycle), which was also specific for MS. Among the cognitive tasks, Alternate Alphabet and Serial Subtracting 7 s were sensitive, whereas Verbal Fluency were both sensitive and specific to CMI in MS. CONCLUSIONS: CMI should be assessed in MS with a standardised dual task such as the Verbal Fluency task while walking, with measurements of the double support time and the effect on the cognitive task. The clinical usefulness of CMI in the assessment of patients with MS is discussed.

Thermoresponsive microgels at the air-water interface: the impact of the swelling state on interfacial conformation.

Poly(N-vinylcaprolactam) (PVCL) is a new temperature-responsive type of polymer microgel with improved biocompatibility as compared to more commonly used poly(N-isopropylacrylamide) (PNIPAM). Both polymers swell at low temperatures and collapse at high ones, showing a volume phase transition temperature (VPTT) around the physiological temperature. Exploring the interfacial characteristics of thermoresponsive microgels is important due to their potential application in emulsion based systems with tailored stabilities and controlled degradation profiles. In this work, we study the properties of charged PVCL particles at the air-water interface by a combination of adsorption, dilatational rheology and Langmuir monolayers. Although PVCL particles adsorb spontaneously at the air-water interface in both, swollen and collapsed conformations, the interfacial properties show significant differences depending on the swelling state. In particular, the total amount of adsorbed microgels and the rigidity of the monolayer increase as the temperature increases above the VPTT, which is connected to the more compact morphology of the microgels in this regime. Dilatational rheology data show the formation of a very loose adsorbed layer with low cohesivity. In addition, collapsed microgels yield a continuous increase of the surface pressure, whereas swollen microgels show a phase transition at intermediate compressions caused by the deformation of the loose external polymer shell of the particles. We also provide a qualitative interpretation for the surface pressure behavior in terms of microgel-microgel effective pair potentials, and correlate our experimental findings to recent rescaling models that take into account the importance of the internal polymer degrees of freedom in the rearrangement of the conformation of the microgel particles at the interface.

Survey of hemostasis management and transfusion in liver transplantation.

OBJECTIVE: To determine the management of haemostasis and transfusion practice in the field of liver transplantation in Spain. METHODS: A questionnaire was developed for physicians in anaesthesiology of all centres performing liver transplantation in Spain. The information required made reference to the 12 months prior to its distribution, from January 1 to December 31, 2011. RESULTS: Data were collected from 24 centres in which liver transplantation is performed in Spain. Only 46% reported that they had protocols or practice guidelines for the management of haemostasis, and 83% of hospitals responded that they knew the percentage of transfused patients, but only 57% knew the mean transfusion. Regarding the degree of satisfaction with the management of haemostasis/coagulation, 50% said they were not satisfied. Thromboelastometry was used as an additional method of preoperative monitoring in only 8% of the centres and intra-operatively in one-third. Less than half (46%) of the centres performed preoperative correction of coagulation deficits based on conventional tests. The mean number of packed red cells used was ≤4 in 57% of centres. Consumption of fresh frozen plasma was highly variable, while 100% of centres consumed less than 4 pools of platelets per patient. CONCLUSIONS: There is a wide variability in the management of haemostasis and transfusion practice among Spanish centres. There are no guidelines or they are not widely used. The mean use of transfused blood products remain high. There was a decrease in centres using new methods of monitoring.

Ion permeation inside microgel particles induced by specific interactions: from charge inversion to overcharging.

In this work we have performed a theoretical study of a system formed by ionic microgels in the presence of monovalent salt with the help of Ornstein-Zernike integral equations within the hypernetted-chain (HNC) approximation. We focus in particular on analysing the role that the short-range specific interactions between the polymer fibres of the microgel and the incoming ions have on the equilibrium ion distribution inside and outside the microgel. For this purpose, a theoretical model based on the equilibrium partitioning effect is developed to determine the interaction between the microgel particle and a single ion. The results indicate that when counterions are specifically attracted to the polymer fibres of the microgel, an enhanced counterion accumulation occurs that induces the charge inversion of the microgel and a strong increase of the microgel net charge (or overcharging). In the case of coions, the specific attraction is also able to provoke the coion adsorption even though they are electrostatically repelled, and so increasing the microgel charge (true overcharging). Moreover, we show that ion adsorption onto the microgel particle is very different in swollen and shrunken states due to the competition between specific attraction and steric repulsion. In particular, ion adsorption occurs preferentially in the internal core of the particle for swollen states, whereas it is mainly concentrated in the external shell for de-swollen configurations. Finally, we observe the existence of a critical salt concentration, where the net charge of the microgels vanishes; above this inversion point the net charge of the microgels increases again, thus leading to reentrant stability of microgel suspensions.

[Use of the Six Sigma methodology for the preparation of parenteral nutrition mixtures]. / Uso de la metodología Seis Sigma en la preparación de mezclas de nutrición parenteral.

OBJECTIVE: To use the tools of the Six Sigma methodology for the statistical control in the elaboration of parenteral nutrition mixtures at the critical checkpoint of specific density. METHODS: Between August of 2010 and September of 2013, specific density analysis was performed to 100% of the samples, and the data were divided in two groups, adults and neonates. The percentage of acceptance, the trend graphs, and the sigma level were determined. A normality analysis was carried out by using the Shapiro Wilk test and the total percentage of mixtures within the specification limits was calculated. RESULTS: The specific density data between August of 2010 and September of 2013 comply with the normality test (W = 0.94) and show improvement in sigma level through time, reaching 6/6 in adults and 3.8/6 in neonates. 100% of the mixtures comply with the specification limits for adults and neonates, always within the control limits during the process. CONCLUSION: The improvement plans together with the Six Sigma methodology allow controlling the process, and warrant the agreement between the medical prescription and the content of the mixture.

Objetivo: Usar las herramientas de la metodología Seis Sigma para el control estadístico de elaboración de mezclas de nutrición parenteral en el punto crítico de control gravimétrico. Métodos: Entre agosto de 2010 y septiembre de 2013 se realizó análisis gravimétrico al 100% de las mezclas dividiendo los datos en dos grupos adultos y neonatos. Se determina el porcentaje de aceptación, las gráficas de tendencia y el nivel de sigma. Se realizo análisis de normalidad con el test Shapiro Wilk y se calcula el porcentaje total de mezclas dentro de límites de especificación. Resultados: Los datos de gravimetría entre agosto de 2010 y septiembre de 2013 cumplen con el test de normalidad (W = 0,94) y presentan mejoramiento en el nivel de sigma a través del tiempo llegando a 6/6 en adultos y 3.8/6 para neonatos. Se logra que el 100% de las mezclas para adultos y neonatos cumplan con límites de especificación, estando siempre dentro de los límites de control del proceso. Conclusión: Los planes de mejoramiento junto a las herramientas de la metodología Seis Sigma permiten controlar el proceso, garantizando la concordancia entre la orden médica y el contenido de la mezcla.

Development and validation of the Spanish Hazard Perception Test.

OBJECTIVE: The aim of the current study is to develop and obtain valid evidence for a hazard perception test suitable for the Spanish driving population. To obtain valid evidence to support the use of the test, the effect of hazardous and quasi-hazardous situations on the participants' hazard prediction is analyzed and the pattern of results for drivers with different driving experience--that is, learner, novice, and expert drivers and reoffender vs. nonoffender drivers--is compared. Potentially hazardous situations are those that develop without involving any real hazard (i.e., the driver did not actually have to decelerate or make any evasive maneuver to avoid a potential collision). The current study analyzed repeat offender drivers attending compulsory reeducation programs as a result of reaching the maximum number of penalty points on their driving license due to repeated violations of traffic laws. METHOD: A new video-based hazard perception test was developed, using a total of 20 hazardous situation videos plus 8 quasi-hazardous situation videos. They were selected from 167 recordings of natural hazards in real Spanish driving settings. RESULTS: The test showed adequate psychometric properties and evidence of validity, distinguishing between different types of drivers. Psychometric results confirm a final version of the hazard perception test composed of 11 video clips of hazards and 6 video clips of quasi-hazards, for which an overall Cronbach's alpha coefficient of.77 was obtained. A lack of ability to detect quasi-hazards and distinguish them from hazardous situations was also found for learner, novice, and reoffender drivers. Learner drivers obtained lower average scores than novice and experienced drivers with the hazardous situation videos, and learner drivers obtained lower average scores than experienced drivers with the quasi-hazardous situation videos, suggesting that the ability to correctly identify hazardous traffic situations may develop early by accumulating initial driving experience. However, the ability to correctly identify quasi-hazardous situations may develop later with the accumulation of further driving experience. Developing this ability is also difficult for reoffender drivers. CONCLUSION: The test has adequate psychometric properties and is useful in distinguishing between learner, novice, and expert drivers. In addition, it is useful in that it analyzes the performance of both safe and unsafe drivers (reoffenders who have already lost their driving license).

Entamoeba histolytica cysteine protease 2 (EhCP2) modulates leucocyte migration by proteolytic cleavage of chemokines.

Human amoebiasis is a disease produced by infection with the protozoan Entamoeba histolytica currently affecting many millions of people worldwide. Amoebic colitis is the most common clinical manifestation. Host protective immunity involves participation of both humoral and cellular responses. However, the mechanisms involved in immune evasion are not clear and remain under investigation. One of these mechanisms could be associated with the ability of parasite proteases to modulate or interfere with the inflammation process, which is initiated by expression of pro-inflammatory cytokines such as chemokines. To further clarify the potential role of cysteine proteases in modulating chemokine-mediated functions, we have analysed the ability of Entamoeba histolytica cysteine protease 2 (EhCP2) to have an effect on the chemotaxis of leucocytes by chemokine cleavage. We find that EhCP2 is capable of cleaving chemokines CCL2, CCL13 and CXCL8, and the resulting proteolysis products modulate the chemotaxis of leucocytes when compared to that induced by intact chemokine. Thus, the extracellular activity of the cysteine proteases affects chemokine-mediated responses and could be considered as part of the mechanisms used by Entamoeba histolytica to circumvent the host immune responses.

Chromosomal changes pattern and gene amplification in T cell non-Hodgkin's lymphomas.

T cell non-Hodgkin's lymphomas are a heterogeneous group of lymphomas with poor prognosis, and whose genetic alterations are not well understood. Comparative genomic hybridization (CGH) is a technique that allows the identification of DNA imbalances without cytogenetic studies. We have studied 37 samples from 29 T cell non-Hodgkin's lymphomas (25 peripheral and four lymphoblastic lymphomas) by CGH in order to detect DNA sequence copy number changes of putative importance in the biology and prognosis of these neoplasms. We detected abnormal CGH profiles in 16/27 (59%) of samples at diagnosis, a ratio that increased to 66% (23/37) when we included the relapsed samples. The most common recurrent changes were gains related to the X chromosome, either the whole chromosome or partially the Xq26-27 bands (19%). Other recurrent changes included gains of bands 9q34, gains of chromosomes 17, 19, and 20, and complete or partial deletions of chromosome 13 (10%). Cancer-related genes located at Xq26-28 region were analyzed by Southern blot and fluorescence in situ hybridization (FISH). Low level amplification of some of these genes was detected by this technique confirming the results obtained by CGH in this region. The detection of abnormal CGH profiles in these T cell lymphomas could have clinical implications. Patients with abnormal CGH profiles showed significant associations with advanced stage of disease, overexpression of P53, and higher proliferative index.

[Giant cyst of the ovary. Report of a case]. / Quiste de ovario gigante. Informe de un caso.

A 38 year old woman nulligravida was admitted with increased abdominal girth for two years, an ultrasound revealed diagnosis of an ovarian cyst, at laparotomy we found a left giant ovarian cyst; hysterectomy was performed, there were no complications. Pathology reports an ovarian serous cystadenoma weighting 30 kg and uterine fibroids, Postoperative course was uneventful. In spite of accessible diagnostic imaging as ultrasound, we still find cases as the one we had described. There has not been reported a mass of this weight in our Institution before.

Topographical characterization and surface force spectroscopy of the photochemical lignin model compound.

By combining the results from atomic force microscopy (AFM) and environmental scanning electron microscopy (ESEM), herein we investigate properties of photochemical lignin model compounds. We provide evidence that photochemical lignin forms random, probably non-functional structures. The topography of such structures is explored using ESEM. Non-functionality of such structures is proved by AFM and atomic force spectroscopy experiments wherein the photochemical lignin functionalized tip is approached to the substrate covered with photochemical lignin. There was no evidence of existence of any kind of host-guest interaction during the approach/retraction experiments. These results provide evidence for our previously stated hypothesis that photochemical lignin polymerization may be one of the degrading effects of UV radiation to the plant cell.

Absence of central microtubules and transposition in the ciliary apparatus of three siblings.

We studied the cases of three siblings with a history of chronic bronchitis and infertility. The electron-microscopic investigation of the tracheal and bronchial biopsies showed a ciliary defect consisting in the absence of the central microtubules and the transposition of a peripheral doublet. This is a rare and infrequently reported abnormality included in the primary ciliary diskinesia syndrome.

The chest radiograph in critically ill surgical patients is inaccurate in predicting ventilator-associated pneumonia.

Chest radiographs (CXRs) are frequently obtained in surgical intensive care unit (SICU) patients when a diagnosis of ventilator-associated pneumonia (VAP) is suspected. The purpose of this study was to determine if the interpretation of the CXR correlated with a diagnosis of VAP in SICU patients. Prospective evaluation of 20 SICU patients clinically suspected of VAP was performed from July 1997 through December 1998. All patients required mechanical ventilation for at least 48 hours, and antibiotic use was discontinued 24 hours before entry into the study. Bronchoscopy with protected specimen brush (PSB) sampling of secretions from the right and left lung was performed. A positive PSB was present if quantitative analysis yielded > or = 10(4) colony-forming units/mL of bacteria. VAP was diagnosed if either the right or left PSB was positive and ruled-out if both the right and left PSB yielded < 10(4) colony-forming units/mL. Twelve of 20 patients (60%) were diagnosed to have VAP by PSB criteria. Eight of 20 patients (40%) had CXRs interpreted as negative for infiltrates; four patients had VAP by PSB criteria. There were four patients with focal infiltrates; two patients had VAP. The remaining eight patients had radiographs interpreted as bilateral infiltrates (one) or pulmonary edema (seven); of these, six patients (75%) had VAP. The sensitivity of the CXR in determining the presence of VAP was 25 per cent, the specificity was 75 per cent, and the accuracy was 0.45. The CXR does not improve the clinician's ability to diagnose VAP: a normal CXR does not exclude the presence of VAP and the finding of a focal infiltrate does not confirm the diagnosis of VAP.