Paving the way for new and challenging matrix reference materials-particle suspensions at the core of material processing providing RMs for method development and method validation.

Sufficient homogeneity of the certified parameter(s) over the whole fill series of a matrix reference material (RM) is a fundamental quality criterion. In practice, the heterogeneity of the target parameter is evaluated, whereby a relative value can be calculated of how much the target parameter is varying over the RM-batch. A high degree of homogeneity (low heterogeneity) is an inherent quality mark of a good RM. Here, we report how challenging matrix RMs were produced by using particle suspensions at the core of the material processing step. The examples of matrix RMs produced span from whole water reference materials for persistent organic pollutants, PM2.5-like atmospheric dust certified for specific ions to microplastic RMs. Most of these RMs were subsequently used in different phases of analytical method development or for method validation. Common to all these matrices is that they cannot be easily mixed, handled, or dosed to prepare larger sample batches. In all cases, a continuously stirred suspension of particles was used during material processing. In general, relative between-bottle heterogeneities from 1.6 to 6% were achieved for the target parameters in these matrix presentations. Concerning developments of new CRMs in emerging fields, the co-dependence between the availability of validated analytical methods with good repeatability and testing materials with a known and high homogeneity of the target parameter(s) becomes particularly challenging. This situation is an RM/Method causality dilemma. To overcome that hurdle, strategies are proposed for stepwise processes where RM producers and a network of analytical method developers could work hand in hand. In addition, development of a portfolio of inexpensive and well-homogenised common samples coupled with a reporting interface is suggested. This would benefit method developers and RM producers alike. As more and more data is compiled for a specific matrix, it paves the way for new and challenging RMs that can later be used by a wider community.

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients.

OBJECTIVE: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. METHOD: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). RESULTS: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p ≤ 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. CONCLUSIONS: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence.

Assisted peritoneal dialysis across Europe: Practice variation and factors associated with availability.

BACKGROUND: In Europe, the number of elderly end-stage kidney disease patients is increasing. Few of those patients receive peritoneal dialysis (PD), as many cannot perform PD autonomously. Assisted PD programmes are available in most European countries, but the percentage of patients receiving assisted PD varies considerably. Hence, we assessed which factors are associated with the availability of an assisted PD programme at a centre level and whether the availability of this programme is associated with proportion of home dialysis patients. METHODS: An online survey was sent to healthcare professionals of European nephrology units. After selecting one respondent per centre, the associations were explored by χ2 tests and (ordinal) logistic regression. RESULTS: In total, 609 respondents completed the survey. Subsequently, 288 respondents from individual centres were identified; 58% worked in a centre with an assisted PD programme. Factors associated with availability of an assisted PD programme were Western European and Scandinavian countries (OR: 5.73; 95% CI: 3.07-10.68), non-academic centres (OR: 2.01; 95% CI: 1.09-3.72) and centres with a dedicated team for education (OR: 2.87; 95% CI: 1.35-6.11). Most Eastern & Central European respondents reported that the proportion of incident and prevalent home dialysis patients was <10% (72% and 63%), while 27% of Scandinavian respondents reported a proportion of >30% for both incident and prevalent home dialysis patients. Availability of an assisted PD programme was associated with a higher incidence (cumulative OR: 1.91; 95% CI: 1.21-3.01) and prevalence (cumulative OR: 2.81; 95% CI: 1.76-4.47) of patients on home dialysis. CONCLUSIONS: Assisted PD was more commonly offered among non-academic centres with a dedicated team for education across Europe, especially among Western European and Scandinavian countries where higher incidence and prevalence of home dialysis patients was reported.

Quality of Life and Autonomy in Patients with Intermittent Bladder Catheterization Trained by Specialized Nurses.

Intermittent bladder catheterization (IBC) involves regular urine draining using a catheter, which is removed immediately after urinary elimination. It allows for the patient's urological health to be managed and their renal function to be preserved, and it promotes autonomy. Compliance with the prescribed number of daily catheterizations, which must be conducted by the patient, and infection prevention measures are crucial. To identify the patients requiring IBC, and to determine their adherence (whether they followed the prescribed guidelines and their difficulty in carrying out the procedure, as well as to assess how the IBC influences their quality of life and state of mind after receiving self-care training from a specialized nurse), we carried out a prospective, multicenter observational study in 24 Spanish hospitals with one month of monitoring and a sample of 99 patients. The sources of information were the patients' clinical records, the King's Health Questionnaire, the Mini-Mental State Examination (MMSE), and the hospital anxiety and depression scale (HADS). Descriptive and bivariate statistics were used to analyses the paired data. After recruitment (n = 99), 79 patients completed the questionnaire at a mean age of 35.2 years (SD = 20.5 years). In total, 53.5% (53) of the sample consisted of men and 32.3% (32) had neurological damage as the reason for prescription; 67% (67.7) performed self-catheterization and 86.7% adhered to the IBC. After one month of monitoring, a statistically significant improvement in quality of life was observed in all criteria, with the exception of personal relationships (p < 0.005), as well as an improvement in anxiety and depression levels (p < 0.001). Patients who require IBC show good adherence to the IBC with a significant percentage of self-catheterization. After one month of IBC, a significant improvement in the patients' quality of life and mood was observed. These results could be attributed to adequate patient training and adequate personalization of the IBC materials by the specialized nurses.

Barriers and opportunities to increase PD incidence and prevalence: Lessons from a European Survey.

INTRODUCTION: Peritoneal dialysis (PD) remains underutilised and unplanned start of dialysis further diminishes the likelihood of patients starting on PD, although outcomes are equal to haemodialysis (HD). METHODS: A survey was sent to members of EuroPD and regional societies presenting a case vignette of a 48-year-old woman not previously known to the nephrology department and who arrives at the emergency department with established end-stage kidney disease (unplanned start), asking which dialysis modality would most likely be chosen at their respective centre. We assessed associations between the modality choices for this case vignette and centre characteristics and PD-related practices. RESULTS: Of 575 respondents, 32.8%, 32.2% and 35.0% indicated they would start unplanned PD, unplanned HD or unplanned HD with intention to educate patient on PD later, respectively. Likelihood for unplanned start of PD was only associated with quality of structure of the pre-dialysis program. Structure of pre-dialysis education program, PD program in general, likelihood to provide education on PD to unplanned starters, good collaboration with the PD access team and taking initiatives to enhance home-based therapies increased the likelihood unplanned patients would end up on PD. CONCLUSIONS: Well-structured pre-dialysis education on PD as a modality, good connections to dedicated PD catheter placement teams and additional initiatives to enhance home-based therapies are key to grow PD programs. Centres motivated to grow their PD programs seem to find solutions to do so.

Analysis of the Financial Impact of Using Cangrelor on the Safety and Efficacy Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Whom Oral Therapy with P2Y12 Inhibitors is Not Feasible or Desirable, in Spain.

PURPOSE: Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in whom oral P2Y12 inhibitors are not feasible or desirable. The objective was to assess the financial impact of introducing cangrelor into the hospital formulary in Spain. PATIENTS AND METHODS: A budget impact model was developed to calculate the cost difference between two scenarios (without and with cangrelor) to treat CAD patients undergoing PCI in whom oral P2Y12 inhibitors are not feasible or desirable, over 3 years. Intravenous P2Y12 inhibitor (cangrelor), oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), and glycoprotein IIb-IIIa inhibitors (GPIs) for bail-out use were considered. Epidemiological, efficacy (thrombotic events including cardiac death), safety (bleeding events), and costs (€, 2019) data were based on Spanish registries, clinical trials, and meta-analyses. One-way sensitivity analysis established the effect of uncertainty on results. RESULTS: For years 1, 2, and 3, the target population to receive cangrelor was 607, 1,822, and 3,340 patients, and cangrelor uptake was 23.70%, 58.30%, and 51.30%, respectively. The 3-year budget impact was 1,021,717€ varying from 50,245€ in year 1 to 599,272€ in year 3. The results were sensitive to the number of patients treated with GPIs in Spanish hospitals. CONCLUSION: Based on our results, the financial effort needed to introduce the use of cangrelor in patients undergoing PCI in whom antiplatelet therapy with oral P2Y12 inhibitors is not feasible or desirable barely exceeds one million € over three years, in Spain.

The bronchial segmentation and its anatomical variations. A clinical-anatomic and bronchoscopy study.

The development in interventional respiratory medicine entails the need of bronchial anatomical knowledge, whose variations assume their greatest importance nowadays. The aim of this study was to describe the frequency of these variations and to analyze the bronchial lengths, barely registered before in literature. This observational descriptive study (from June 2018 until April 2019) was conducted in a sample of 17 pairs of lungs, which were dissected and measured at the Cadaver Donation Centre (Universidad Complutense, Madrid), and a second sample of 50 bronchoscopies, performed at the San Carlos Clinic Hospital, which were analyzed during the procedure. Our results show that there are no significant differences in the incidence of variations by sex in any of both samples, and neither in the average length of any bronchus by sex nor lobar pattern. Left main bronchus presents the longest length and left upper lobe bronchus the shortest. The highest percentage of variations is contained in the right lower lobe (25.4%), and the most frequent variation in the subsuperior bronchus (B*) (19.4%). The middle lobe and the left lower lobe present the lowest percentage of variations (11.9%). Only 37.3% of the pairs of lungs/patients did not have any anatomical variation in the general sample. Despite of the small size of the sample, results show a high percentage of variations and a minority of completely normal pairs of lungs, which invites us to reflect about the probable high prevalence of variations in the general population. Further studies with greater samples are needed to confirm our hypothesis.

Measuring Smoothness as a Factor for Efficient and Socially Accepted Robot Motion.

Social robots, designed to interact and assist people in social daily life scenarios, require adequate path planning algorithms to navigate autonomously through these environments. These algorithms have not only to find feasible paths but also to consider other requirements, such as optimizing energy consumption or making the robot behave in a socially accepted way. Path planning can be tuned according to a set of factors, being the most common path length, safety, and smoothness. This last factor may have a strong relation with energy consumption and social acceptability of produced motion, but this possible relation has never been deeply studied. The current paper focuses on performing a double analysis through two experiments. One of them analyzes energy consumption in a real robot for trajectories that use different smoothness factors. The other analyzes social acceptance for different smoothness factors by presenting different simulated situations to different people and collecting their impressions. The results of these experiments show that, in general terms, smoother paths decrease energy consumption and increase acceptability, as far as other key factors, such as distance to people, are fulfilled.

Factores ambientales que influyen en la ictiofauna de la laguna La Mancha, sitio Ramsar, Golfo de México / Environmental factors influencing the ichthyofauna of the La Mancha lagoon, Ramsar site, Gulf of Mexico

Resumen La laguna La Mancha en el Golfo de México, es un sistema costero con categoría Ramsar por su alta biodiversidad, numerosas especies de peces dependen de el para realizar sus ciclos de vida. Fue analizada la variación espacial y temporal de la diversidad, abundancia y asociaciones de peces y su relación con los factores fisicoquímicos. Entre abril de 2005 y enero de 2008, se realizaron 95 muestreos diurnos en siete sitios donde se registraron las características del agua y la composición de la comunidad de peces. El sistema presentó variaciones espacio temporales de los parámetros físicoquímicos, definiendo ambientes contrastantes de acuerdo con los gradientes locales. Se recolectaron 5 974 individuos, pertenecientes a 50 especies, 39 géneros y 25 familias, cuatro especies son registros nuevos para el sistema. La diversidad y riqueza de especies fueron altas en el ambiente salobre y bajos en zonas dulceacuícolas. En septiembre (lluvias) y noviembre (nortes) la diversidad (H' = 1.52) y riqueza (D = 1.99) fue más alta. La abundancia de los peces fue mayor hacia la boca de conexión con el mar. La densidad y biomasa (1.17 indiv./m2, 4.33 g/m2) fue mayor en abril (secas) y el peso promedio (30.82 g/ind) en julio (lluvias). El Índice de Valor de Importancia (IVI) definió cuatro especies dominantes que representan el 75 % de la abundancia numérica y el 46 % de la captura total en peso. El Análisis de Correspondencia Canónica (ACC) mostró que la relación peces-hábitat fue explicada en un 57 % de la varianza total para los primeros dos ejes, donde las variaciones de temperatura, salinidad, oxígeno disuelto y profundidad fueron los factores ambientales que determinaron la composición, distribución, componentes comunitarios y categorías tróficas de los peces en la comunidad. Este estudio aporta información sobre la relación del ambiente con la estructura de la comunidad íctica de La Mancha, y representa una base para realizar monitoreo ecológico que permita incrementar el conocimiento necesario sobre el ecosistema y sus poblaciones de peces, con la finalidad de proponer estrategias de manejo para la conservación de los recursos pesqueros de Veracruz.

Abstract La Mancha lagoon in the Gulf of Mexico, is a coastal system with Ramsar category because of its high biodiversity, many species of fish depend on it to complete their life cycles. In this study we analyzed the spatial and temporal variation of fish diversity, abundance and associations, and its relationship with physicochemical factors. Between April 2005 and January 2008, 95 daytime samplings were carried out at seven sites, where water characteristics and the composition of fish community were recorded. The system presented spatial-temporal variations of the physicochemical parameters, defining contrasting environments according to the local gradients. A total of 5 974 fish individuals, belonging to 50 species, 39 genera and 25 families were collected; four species were new records for the system. The diversity and richness of species were high in the brackish environment and low in freshwaters areas. In September (rainy season) and November ("nortes" season), diversity (H' = 1.52) and richness (D = 1.99) were highest. Fish abundance was greater towards the mouth connecting with the sea. The density and biomass (1.17 ind/m2, 4.33 g/m2) was higher in April (dry season) and the average weight (30.82 g/ind) in July (rainy season). The Importance Value Index (IVI) defined four dominant species representing 75 % of the numerical abundance and 46 % of the total catch in weight. The Canonical Correspondence Analysis (CCA) showed that the fish-habitat relationship was explained in 57 % of the total variance for the first two axes, where the variations in temperature, salinity, dissolved oxygen and depth were the environmental factors that determined the composition, distribution, community components and trophic categories of the fish community. This study provides information on the relationship between the environment and the structure of the fish community in La Mancha, and represents a basis for ecological monitoring to increase the knowledge needed about the ecosystem and fish populations, in order to boost management strategies for the fishery resources conservation in Veracruz. Rev. Biol. Trop. 66(1): 246-265. Epub 2018 March 01.

Melatonin's role as a co-adjuvant treatment in colonic diseases: A review.

Melatonin is produced in the pineal gland as well as many other organs, including the enterochromaffin cells of the digestive mucosa. Melatonin is a powerful antioxidant that resists oxidative stress due to its capacity to directly scavenge reactive species, to modulate the antioxidant defense system by increasing the activities of antioxidant enzymes, and to stimulate the innate immune response through its direct and indirect actions. In addition, the dysregulation of the circadian system is observed to be related with alterations in colonic motility and cell disruptions due to the modifications of clock genes expression. In the gastrointestinal tract, the activities of melatonin are mediated by melatonin receptors (MT2), serotonin (5-HT), and cholecystokinin B (CCK2) receptors and via receptor-independent processes. The levels of melatonin in the gastrointestinal tract exceed by 10-100 times the blood concentrations. Also, there is an estimated 400 times more melatonin in the gut than in the pineal gland. Gut melatonin secretion is suggested to be influenced by the food intake. Low dose melatonin treatment accelerates intestinal transit time whereas high doses may decrease gut motility. Melatonin has been studied as a co-adjuvant treatment in several gastrointestinal diseases including irritable bowel syndrome (IBS), constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D), Crohn's disease, ulcerative colitis, and necrotizing enterocolitis. The purpose of this review is to provide information regarding the potential benefits of melatonin as a co-adjuvant treatment in gastrointestinal diseases, especially IBS, Crohn's disease, ulcerative colitis, and necrotizing enterocolitis.

Dock10 regulates CD23 expression and sustains B-cell lymphopoiesis in secondary lymphoid tissue.

Dock10, a guanine nucleotide exchange factor for the Rho GTPases Rac1 and Cdc42, affects cell morphology, membrane protrusive activity, and cell movement. Dock10 is prominently expressed in lymphoid tissue and upregulated by IL-4 in B cells. To investigate the physiological role of Dock10, WT mice and Dock10 KO mice were used. KO mice showed decreased numbers of B cells in spleen, both follicular B cells and marginal zone B cells, and in peripheral blood, but not in bone marrow. The antiapoptotic effect of IL-4 in vitro, the migratory response to CXCL13 or CCL21 in vitro, and the whole genome expression profile were intact in spleen B cells from KO mice. CD23, the low-affinity receptor for immunoglobulin E, was overexpressed on follicular B cells from KO mice, suggesting that Dock10 negatively regulates membrane CD23 expression. Negative regulation of CD23 expression by Dock10 could play a role in B cell maturation and function.

[NURSING CARE PROTOCOL ON MANAGEMENT OF RADIODERMITIS]. / ProtocoLo de cuidados de enfermería en el tratamiento de la radiodermitis.

INTRODUCTION: Cases of radiation recall may be experienced by radiotherapy patients, which are named as radiodermitis. To gradate it the RTOG (Radiation Therapy Oncology Group) scale is the most used. Due to the complexity on the management of radiotherapy, a protocol based on the evidence is stablished to prevent and treat it. MATERIAL AND METHODS: Bibliographic revision of main data bases from last six years. RESULTS: 14 different studies which have the criteria for their inclusion are selected. These studies will gather, with different levels of evidence, several prevention and treatment methods and products for radiodermitis. DISCUSSION: To prevent it from happening, it is a must to clean and dry the skin appropriately. Urea, hyaluronic acid and Tex-OE based creams have shown their effectiveness on grades 0-1. Regarding treatment, the use of medium-high corticoids, the barrier creams, silver sulfadiazine, hyaluronic acid and no sting barrier film can reduce the gravity of the wounds. The use of the healing in humid environments is also recommended on the treatment of radiodermitis. Some products like hydrocolloids, silver dressings and hydrogel also improve the scarring. CONCLUSION: Managing radiodermitis is a complex matter. Therefore the action protocol based on evidence is the ideal tool to improve the efficiency and effectiveness of the cares, giving an increase on the tolerance to treatment and a reduction on the public health cost and a higher quality of life fo rpatients.

The impact of interventional nephrologists on the growth of a peritoneal dialysis program: Long-term, single-center experience.

Peritoneal dialysis (PD) is an underutilized form of renal replacement therapy. Although a variety of factors have been deemed responsible, timely insertion of a PD catheter may also be a contributory factor. Furthermore, a good catheter implantation technique is important to allow for effective peritoneal access function and long-term technique survival. Studies regarding results obtained by nephrologists in comparison with surgeons have been limited to small single-center experiences. Thus, the objective of this study was to explore the impact of the peritoneal dialysis (PD) catheter insertion by nephrologists compared to surgeons on early catheter complications and on technique survival. We also examine whether PD catheter insertion by nephrologists has a positive impact on the growth in the number of patients using PD. We performed 313 consecutive procedures: 192 catheter insertions and 121 catheter removal from January 1, 2006 to December 31, 2013. The main reasons for catheter removal were: renal transplantation, 52 (43%) follow of transfer to HD, 48 (40%) and catheter malfunction, 16 (13%). The patients were mostly male (63.4%) with the mean age of 50.8±15.1 years and 23.8 were diabetics. We only observed seven (2.5%) early complications (<4 weeks) associated to peritoneal catheter surgery (3 peritonitis episodes, 2 hemoperitoneum episodes, one complicated hernia and one omental entrapment). There were not significant differences in surgery-related complications in both periods. The penetration ratio of PD after 2006 was 117% higher compared with procedures performing before this date. In conclusions, we have demonstrated a positive impact on the growth of the PD population when catheter insertion is performed by nephrologists with a minimal incidence of complications associated.

Social robots in advanced dementia.

AIMS: Pilot studies applying a humanoid robot (NAO), a pet robot (PARO) and a real animal (DOG) in therapy sessions of patients with dementia in a nursing home and a day care center. METHODS: In the nursing home, patients were assigned by living units, based on dementia severity, to one of the three parallel therapeutic arms to compare: CONTROL, PARO and NAO (Phase 1) and CONTROL, PARO, and DOG (Phase 2). In the day care center, all patients received therapy with NAO (Phase 1) and PARO (Phase 2). Therapy sessions were held 2 days per week during 3 months. Evaluation, at baseline and follow-up, was carried out by blind raters using: the Global Deterioration Scale (GDS), the Severe Mini Mental State Examination (sMMSE), the Mini Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), the Apathy Scale for Institutionalized Patients with Dementia Nursing Home version (APADEM-NH), the Apathy Inventory (AI) and the Quality of Life Scale (QUALID). Statistical analysis included descriptive statistics and non-parametric tests performed by a blinded investigator. RESULTS: In the nursing home, 101 patients (Phase 1) and 110 patients (Phase 2) were included. There were no significant differences at baseline. The relevant changes at follow-up were: (Phase 1) patients in the robot groups showed an improvement in apathy; patients in NAO group showed a decline in cognition as measured by the MMSE scores, but not the sMMSE; the robot groups showed no significant changes between them; (Phase 2) QUALID scores increased in the PARO group. In the day care center, 20 patients (Phase 1) and 17 patients (Phase 2) were included. The main findings were: (Phase 1) improvement in the NPI irritability and the NPI total score; (Phase 2) no differences were observed at follow-up.

IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.

Interleukin 4 (IL-4) induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL) cells. MicroRNAs (miRNAs) regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC), and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p), miR-500a (3p), miR-502 (3p), and miR-532 (3p and 5p) genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.

Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells.

Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been recently cloned. Here, we address GTPase specificity and GEF activity of Dock10. In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1, Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a morphologic change in two-dimensional culture consisting in loss of cell elongation, increase of filopodia, and ruffles. Area in contact with the substrate of cells that spread with non-elongated morphology was larger in cells expressing Dock10. Inducible expression of constitutively active mutants of Cdc42 and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of adherent HeLa cells.

Condiciones violentas de duelo y pérdida: un enfoque psicoanalítico / Violent Circumstances of Grief and Loss: A Psychoanalytical Approach / Condições violentas de luto e perda: um enfoque psicanalítico

El objetivo de este artículo es reflexionar y analizar, desde un punto de vista psicoanalítico, el tema de la imposibilidad del duelo pensado a partir de la experiencia de las pérdidas (entendidas estas en su dimensión más fatídica), de seres amados arrebatados por la violencia; en particular, lo referente a la relación del duelo con el trauma y el reclamo de los cuerpos desaparecidos. Esto es revisado a partir de la necesidad de abordar una de las problemáticas actuales en México que se imponen a la mirada y estudio de la psicología y el psicoanálisis. Para ello, se hace uso de diversos métodos de análisis teórico y discursivo, ubicando a Freud como principal referente teórico. El resultado es el encuentro de discursos repetidos de dolor, que delatan una imposibilidad de efectuación del duelo, del ritual de la pérdida, del trauma y de la insuficiencia de la palabra. A partir de esta posición de complicación subjetiva ante la pérdida, se da cuenta de la incursión del no-lugar del duelo al producirse una pérdida particular que le implique al sujeto enfrentarse tanto con la muerte del otro como a la de sí mismo.

The objective of this study is to reflect and analyze, from a psychoanalytical perspective, the difficulty in adapting emotionally to the experience of loss (understood in its most fatidical dimension) of loved ones who have been taken from us through violence, particularly with regard to the relationship between grief and trauma, and the search for those persons who are missing. This study is being undertaken due to the need to tackle one of the most pressing problem areas in Mexico, which requires consideration and study on the part of psychology and other sciences. To accomplish this, diverse psychoanalytic theoretical and discursive methods are used, with Freud as the main theoretical reference. The results reveal repeated reports of pain that evidence the inability to assume the process of grieving, together with the associated trauma and the inadequacy of words. From this position of subjective complication when faced with loss, the absence of an opportunity to complete the grieving process when a personal loss occurs becomes evident, which implies that the subject has to deal with the death of the other person as well as his own.

O escopo de este artigo e reflexionar e analisar, desde um ponto de vista psicanalítico, o tema da impossibilidade do luto pensado a partir da experiência das perdas (entendidas na sua dimensÃo mais fatídica) de seres amados arrebatados pela violência, em particular o referente com a relaçÃo do luto com o trauma e o reclamo dos corpos desaparecidos. Isto é revisado a partir da necessidade de abordar uma das problemáticas atuais no México que se impõem na mirada e estudo da psicologia e o psicanálise. SÃo ocupados diversos métodos de análise teórico e discursivo, colocando ao Freud como principal referente teórico. O resultado é o encontro de discursos repetidos de dor que delatam uma impossibilidade de efetuaçÃo de luto, do ritual da perda, do trauma e da insuficiência da palavra. A partir de esta posiçÃo de complicaçÃo subjetiva ante a perda, damos conta da incursÃo do nÃo-lugar do luto no momento da perda particular que implique para o sujeito enfrentara morte do outro e a mesma própria.

Sistemática para el estudio Doppler de carótidas / Systematic assessment in carotid doppler ultrasound

La exploración de los ejes carotideo y vertebral resulta sencilla técnicamente, con un aprendizaje relativamente rápido para el que inicia la actividad, especialmente si se establecen protocolos de exámenes estandarizados y fácilmente reproducibles. El objetivo de la sistematización en los servicios de Doppler vascular es que los exámenes realizados por distintos operadores sean similares en cuanto a la técnica y la terminología del informe; a nivel docente la sistematización ofrece al neófito una metodología clara a seguir con el fin de completar las evaluaciones y solidificar el proceso de aprendizaje.

The gene expression response of chronic lymphocytic leukemia cells to IL-4 is specific, depends on ZAP-70 status and is differentially affected by an NFκB inhibitor.

Interleukin 4 (IL-4), an essential mediator of B cell development, plays a role in survival of chronic lymphocytic leukemia (CLL) cells. To obtain new insights into the function of the IL-4 pathway in CLL, we analyzed the gene expression response to IL-4 in CLL and in normal B cells (NBC) by oligonucleotide microarrays, resulting in the identification of 232 non-redundant entities in CLL and 146 in NBC (95 common, 283 altogether), of which 189 were well-defined genes in CLL and 123 in NBC (83 common, 229 altogether) (p<0.05, 2-fold cut-off). To the best of our knowledge, most of them were novel IL-4 targets for CLL (98%), B cells of any source (83%), or any cell type (70%). Responses were significantly higher for 54 and 11 genes in CLL and NBC compared to each other, respectively. In CLL, ZAP-70 status had an impact on IL-4 response, since different sets of IL-4 targets correlated positively or negatively with baseline expression of ZAP-70. In addition, the NFκB inhibitor 6-Amino-4-(4-phenoxyphenethylamino)quinazoline, which reversed the anti-apoptotic effect of IL-4, preferentially blocked the response of genes positively correlated with ZAP-70 (e.g. CCR2, SUSD2), but enhanced the response of genes negatively correlated with ZAP-70 (e.g. AUH, BCL6, LY75, NFIL3). Dissection of the gene expression response to IL-4 in CLL and NBC contributes to the understanding of the anti-apoptotic response. Initial evidence of a connection between ZAP-70 and NFκB supports further exploration of targeting NFκB in the context of the assessment of inhibition of the IL-4 pathway as a therapeutic strategy in CLL, especially in patients expressing bad prognostic markers.

Motor effects of radio electric asymmetric conveyer in Alzheimer's disease: results from a cross-over trial.

We conducted a randomized, cross-over trial to investigate the feasibility, safety, and motor effects of brain stimulation with radio electric asymmetric conveyer (REAC) technique in patients with Alzheimer's disease (AD). Neuropostural optimization (NPO) and sham protocol were administered to 60 patients from the nursing home and day care units of the Alzheimer Center Reina Sofía Foundation. The mean age was 84.1 (SD 7.9) years and 86.7% of the subjects were female. Motor measures were collected at baseline (T1), immediately (T2), seven (T3), and 11 days (T4) after treatment and, following cross-over, immediately (T5), seven (T6), and 11 (T7) days after treatment. Close safety surveillance was conducted from seven days before T1 to the end of the study (T7), with total study duration of 35 days. Wilcoxon test was utilized in the efficacy analysis, considering T1 and T5 as independent baseline assessments and using a threshold of p < 0.05 (corrected) for statistical significance. The NPO protocol was easily administered and well accepted by the participants. Axial movements improved at T3 and T4 after NPO and at T2 after sham NPO, but no significant effects were observed in axial movements in the second phase of the trial. The effects of NPO in gait performance were not consistent. There were six falls between T2 and T7, but only two of them occurred in patients who had received NPO. In light of safety and feasibility of REAC, a trial with the more intense neuropsycho-physical optimization protocol is warranted.