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Background and objective Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune disease with clinical characteristics that show geographic variations. However, these differences between regions have not been fully described; therefore, the objective of this study is to describe the clinical and sociodemographic characteristics of Cuban patients with SLE. Patients and methods 149 patients with SLE and 151 with other systemic autoimmune diseases were studied. Sociodemographic and clinical characteristics according on the criteria of the American College of Rheumatology of 1997 were identified. To evaluate the associations between clinical manifestations and SLE, a logistic regression analysis was performed; the odds ratio (OR) was calculated with its corresponding 95% confidence interval and the method of multiple correspondence analysis was also used. By an analysis of the configurations of frequency the typical combinations of criteria related to the patients with SLE were identified. Results The most frequent criteria in SLE were immunological disorders (85.2%). ANA positive (85.2%) arthritis (78.5%), photosensitivity (77.2%), and malar rash (61%). The renal involvement and immunological disorders criteria were the best (highest OR) at discriminating SLE patients. The combination of only three criteria (malar rash, positive ANA, and immunological disorder) could be enough to classify a homogeneous population. Conclusions This study enabled us to determine the main clinical characteristics of patients with SLE in Cuba. This information could be useful to improve the efficiency of SLE diagnosis and facilitate more specific treatments.

Introduction and objectives Risk stratification of ventricular arrhythmias in patients with repaired tetralogy of Fallot (rTOF) remains unresolved. We aimed to identify right ventricular (RV) electrophysiological parameters potentially associated with a higher risk of ventricular arrhythmias in patients with rTOF. Methods We included all consecutive patients with rTOF who underwent RV electroanatomical mapping at a single tertiary center. We used logistic regression modeling to identify those variables associated with an increased risk of clinical or induced ventricular tachycardia (VT), or clinical VT exclusively. Results Twenty-one of the 56 patients included had clinical or induced VT. A high-frequency of premature ventricular contractions/nonsustained VT (OR, 11.34; 95%CI, 1.50-85.97; P = .019), an HV interval > 55 ms (OR, 21.20; 95%CI, 3.12-144.14; P = .002), and RV activation time (ms) (OR [per 10 ms intervals], 1.34; 95%CI, 1.02-1.75; P = .035) proved to be associated with clinical or induced VT. The model including this information had good discrimination ability, with an area under the curve of 0.884 (95%CI, 0.79-0.97; P 55 ms (OR, 9.65; 95%CI, 1.41-66.14; P = .021) and high-frequency of premature ventricular contractions/nonsustained VT (OR, 13.14; 95%CI, 1.95-88.54; P = .008) were independently associated (area under the curve of 0.836 [95%CI, 0.663-1.000; P = .002]). Conclusions High-frequency of premature ventricular contractions/nonsustained VT, an HV interval > 55 ms and RV activation time are factors associated with an increased risk of ventricular arrhythmias in patients with rTOF.

O objetivo do presente artigo é apresentar as principais concepções de “aprendizagem da docência” em trabalhos nacionais no campo da formação de professores, produzidos de 2010 a 2020, e resultados de pesquisas fundamentadas nessas concepções. Realizamos uma revisão sistemática da literatura sobre a “aprendizagem da docência” de futuros professores; professores da educação básica e professores do ensino superior. Consultamos as bases de dados da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e Scientific Eletronic Library Online – Scielo, além dos anais eletrônicos dos principais eventos científicos nacionais relacionados à formação de professores. Foram identificados e analisados: artigos científicos publicados em periódicos nacionais; trabalhos constantes nos anais especificados; capítulos de livros e livros. Concluímos que: a) a categoria “aprendizagem da docência” refere se às aprendizagens específicas do professor em sua prática pedagógica, sobre, na e para a docência; b) há a predominância de seis concepções específicas sobre a “aprendizagem da docência”; c) essas concepções se articulam com diferentes campos do conhecimento d) os aspectos comuns dos resultados das pesquisas podem contribuir para avanços na definição da categoria “aprendizagem da docência” no campo da formação de professores; e) a pesquisa colaborativa, interventiva e as narrativas dos professores são vias metodológicas importantes à compreensão de como ocorre a “aprendizagem da docência” e à promoção desse processo.

Patients with a single syncopal episode (SSE) and complete bundle branch block (cBBB) are frequently managed more conservatively than patients with recurrent episodes (RSE). The objective of this study was to analyze if there are differences between patients with single or recurrent unexplained syncope and cBBB in arrhythmic risk, the diagnostic yield of tests, and clinical outcomes.Cohort study of consecutive patients with unexplained syncope and cBBB with a median follow-up time of 3 years. The patients were evaluated via a stepwise workup protocol based on electrophysiological study (EPS) and long-term follow-up with an implantable cardiac monitor.Of the 503 patients included in the study, 238 (47.3%) had had only 1 syncopal episode. The risk of an arrhythmic syncope was similar in both groups (58.8% in SSE vs 57.0% in RSE; P = .68), also after adjustment for possible confounding variables (HR, 1.06; 95%CI, 0.81-1.38; P = .674). No significant differences between the groups were found in the EPS results and implantable cardiac monitor diagnostic yield. A total of 141 (59.2%) patients with SSE and 154 (58.1%) patients with RSE required cardiac device implantation (P = .797). After appropriate treatment, 35 (6.7%) patients had recurrence of syncope. The recurrence rate and mortality were also similar in both groups.Patients with cBBB and unexplained syncope are at high risk of an arrhythmic etiology, even after the first syncopal episode. Patients with SSE and RSE have a similar arrhythmic risk and similar outcomes, and therefore there is no clinical justification for not managing them in the same manner.

Cet article porte sur l’analyse iconographique de Four seasons (1993), par l’artiste contemporain Edwin Parker “Cy Twombly” (Cy Twombly, 1928 – 2011), à la lumière de deux créations du maître impressionniste Pierre-Auguste Renoir (1845 – 1919). La vague (1879) et Paysage bords de Seine (1879) sont deux œuvres où Renoir imprime un sceau qui capte l’éphémère à travers la couleur, le mouvement de la lumière et le pleinairisme. Four seasons est une œuvre qui ne peut pas être comprise comme création contemporaine sans étudier l’empreinte de Renoir dans l’abstraction lyrique américaine ̶ un sceau visible dans la technique, l’usage de la couleur, la thématique et le message de la création. Le besoin de saisir l’harmonie, à travers une création dans laquelle l’image et le texte se mêlent, représente l’évolution de la même œuvre de Renoir dans la contemporanéité : une création où le message unit image et langage, voire un poème visuel.

In recent years, the conceptual advancement on green analytical chemistry (GAC) has moved in parallel with efforts to incorporate new screening or quantitative low-cost analytical tools to solve analytical problems. In this sense, the role of solid state techniques that allow the non-invasive analysis (or with a minimum sample treatment) of solid samples cannot be neglected. This review describes the basic principles, instrumentation and advances in the application of X-ray fluorescence instrumentation to the environmental sciences research topics, published between 2006 and 2020. Obviously, and because of the enormous number of works that can be found in the literature, it is not possible to exhaustively cover all published articles and the diversity of topics related to the environment in which a solid state technique like XRF has been applied successfully. It is a question of making a compilation of the instrumentation in use, the significant advances in XRF spectrometry and sample treatment strategies to highlight the potential of its implementation for environmental assessment., This work has been carried out within the framework of the activities of the Grant CEX2018-000794-S, funded by MCIN/AEI/10.13039/501100011033, Ministry of Science and Innovation, Spain.

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.

In this contribution, the analytical potential of total reflection X-ray fluorescence (TXRF) instrumentation has been evaluated for the determination of major and trace elements in milk powder. TXRF allows the possibility of direct analysis of solid suspensions without the need for a digestion process and therefore it can be a potential analytical candidate for simple and cost-effective analysis. A detailed study to select sample preparation and measurements conditions was carried out. Different quantification approaches (including internal standardization and empirical calibration) were also tested. Finally, the developed TXRF methods (W anode) were validated by a strict comparison with the data from the reference methods on a set of twenty-three samples using robust statistics. Results showed that acceptable results can be obtained for K, Ca, Fe and Zn determination if using adequate calibration approaches. Otherwise, only screening results can be obtained for light elements (P and Cl) in milk powder samples., Eduard Roura is acknowledged for his support in the laboratory work. Ignasi Queralt also acknowledges the “Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033”.

Aim: to explore and describe the experiences of women giving birth in a tertiary public hospital, with special focus on experiences related to humanized care and women's participation in decision making. Method: this is a qualitative phenomenological study through semi-structured interviews to postpartum women giving birth in a tertiary hospital between January and May 2017. Data were analysed through content analysis. Results: the two overarching themes emerged were the professional-information dyad and privacy. Subthemes of the first main theme were the therapeutic relationship, decision-making, feeding the baby, procedures, and the time factor. Subthemes of the second topic were the feelings generated by the hospital environment, the delivery room, and the maternity ward. Conclusions: if the therapeutic relationship is good, technology is not seen as dehumanising but rather as necessary to ensure continuing safety. "Humanising" material resources are not a priority for women in the birth process and are little used. Privacy was experienced as being a particularly intense need, which women called for throughout the healthcare process.

Introduction and objectives: This report presents the findings of the 2018 Spanish Catheter Ablation Registry. Methods: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers. Results: Data sent by 100 centers were analyzed, with a total number of 16,566 ablation procedures performed (the highest historically reported in this registry) for a mean of 165.5 ± 127.9 and a median of 119 procedures per center. The ablation targets most frequently treated were atrial fibrillation (n = 4234; 25.6%), atrioventricular nodal re-entrant tachycardia (n = 3525; 21.3%) and cavotricuspid isthmus (n = 3425; 20.7%). A new peak was observed in the ablation of atrial fibrillation, increasing the distance from the other substrates. The overall success rate was 91%. The rate of major complications was 2.2%, and the mortality rate was 0.04%. A total of 2.1% of the ablations were performed in pediatric patients. Conclusions: The Spanish Catheter Ablation Registry systematically and continuously enrolls the ablation procedures performed in Spain, showing a progressive increase in the number of ablations over the years, with a high success rate and low percentage of complications.

Resumen Los sincopes y otras perdidas transitorias de conocimiento son una patologia frecuente en los ancianos que tambien aparecen como caidas inexplicadas. La historia clinica, exploracion fisica, determinaciones de tension arterial en ambos brazos y ortostatica, electrocardiograma y analitica, si procede, son las pruebas iniciales fundamentales en su valoracion. Las causas de los sincopes son variadas, desde la patologia estructural cardiaca, arritmias, sincopes reflejos como el vasovagal, situacionales, sindrome del seno carotideo e hipotension ortostatica, hasta los no sincopales como la epilepsia, las hipoglucemias, los trastornos metabolicos o los pseudosincopes psicogenos. El manejo posterior se basa en la valoracion geriatrica y la evaluacion de la fragilidad, determinacion de si fue sincope, busqueda de la causa y estratificacion del riesgo. Es frecuente encontrar mas de una causa o factor predisponente. En ancianos fragiles, las dificultades para la sospecha clinica favorecen el empleo de pruebas complementarias que suelen ser bien toleradas. Syncope and other transitory losses of consciousness are common disorders in elderly people that also occur as unexplained falls. Clinical history, physical examination, blood pressure measurement in both arms and orthostatic measurement, electrocardiogram and blood analyses, if it is indicated, are the essential initial tests in their assessment. Syncope has various causes, from structural heart diseases, arrhythmia, reflex syncopes such as vasovagal syncope, situational syncope, carotid sinus syndrome and orthostatic hypotension, to non-syncopal conditions such as epilepsy, hypoglycaemia, metabolic disorders or psychogenic pseudosyncope. Subsequent management is based on the geriatric assessment and assessment of frailty, determining syncope, looking for the cause and stratifying risk. It is common to find more than one cause or predisposing factor. In frail elderly people, complementary tests that are usually well tolerated can assist with the difficulties in clinical suspicion.

BACKGROUND: Repeated implantable cardioverter‐defibrillator (ICD) therapies cause myocardial damage and, thus, an increased risk of arrhythmias and mortality. HYPOTHESIS: Cardiac resynchronization therapy–defibrillator (CRT‐D) reduces the number of appropriate therapies in patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] 35% at the end of follow‐up had a significantly lower risk of receiving a first appropriate therapy relative to those with an ICD (adjusted hazard ratio: 0.24, 95% confidence interval: 0.07–0.83, P = 0.025), independently of ischemic cardiomyopathy, baseline LVEF, and secondary prevention. There were no differences in mortality between the ICD and the CRT‐D groups. CONCLUSIONS: Although patients receiving CRT‐D had a worse clinical profile, they received fewer device therapies in comparison with those receiving an ICD. This reduction is associated with a significant improvement in LVEF.

IntroductionAgitation and violent behaviours are common conditions developed by patients with acute traumatic brain injury (TBI) in intensive care units (ICUs). Healthcare professionals caring for these patients have various tools to manage these behaviours, but lack of a formal protocol to assess and manage them makes caring for these patients a challenge. Moreover, safety may often be compromised for both ICU professionals and patients encountering such situations. The EXperienceS and aTtitudes towards Agitated behaviours in Traumatic brain injury in the Intensive Care unit patients (EXSTATIC) study aims to explore the experiences and attitudes of ICU nurses and other ICU healthcare professionals on the management of agitated behaviours in patients with acute TBI.Methods and analysisEXSTATIC is a multicenter mixed methods convergent study exploring experiences and attitudes of ICU healthcare professionals caring of agitated patients with TBI. The study includes three qualitative methods (observation, semistructured interviews and focus groups) and one quantitative method (retrospective cohort). The integration of the different methods will be done using sequential steps of the research and by the integration of results for each step. Qualitative data will be evaluated following a thematic analysis derived from a grounded theory approach. Quantitative data will be analysed using descriptive statistics. Qualitative and quantitative results will be combined in a convergent interactive interpretative design. Gender and race perspective will be integrated in collection, analysis and interpretation of data.Ethics and disseminationThis study has been approved by the Centre intégré universitaire de santé et de services sociaux du nord de l’île de Montréal (CIUSSS-NÎM) Research Ethics Board. The findings will be disseminated locally with ICU staff and health managers, international peer-reviewed journals, a PhD dissertation, and national and international conferences. The knowledge derived from this study is key in the development of clinical protocols to manage agitation and related behaviours in patients with TBI and designing further interventional studies targeting this specific problematic.Trial registration numberNCT04741399.

Paullinia cupana var. sorbilis (Mart.) Ducke, popularly known as guarana, is one of the most promising plants in Brazilian flora and has attracted considerable interest from the scientific community owing to its numerous therapeutic activities and less side effects. Hence, using nanotechnology is a viable alternative to primarily improve the physicochemical characteristics and bioavailability of guarana. The objective of the present study was to develop, characterize, and evaluate the stability of liposomes containing guarana powder and to evaluate their antioxidant and hemolytic activity in vitro. Three different concentrations of guarana powder and two methods of liposome preparation were tested. Liposomes were developed and characterized, and their stability was analyzed by evaluating physicochemical parameters. Hemolytic activity of guarana liposomal formulation (G-Lip) was compared with that of guarana in its free form (FG) and of liposome without guarana (W-Lip). Red blood cells from rats were exposed to these different formulations dissolved in phosphate buffer solution (PBS; pH 7.4). The best stability was achieved for the formulation containing 1 mg mL−1 guarana powder produced by the reverse phase evaporation method. FG showed dose-dependent antioxidant activity, which was maintained in G-Lip. W-Lip showed high hemolytic activity in PBS at pH 7.4 possibly because of the presence of polysorbate 80, and on addition of guarana to these structures, the hemolytic process was reversed. The same protective effect was observed for FG. It is believed that the complex structure of guarana, primarily the presence of polyphenols, exerts a powerful antioxidant action, helping to protect erythrocytes.

We evaluate the effect of cationic nanocapsules containing dihydromyricetin (DMY) flavonoid for safe topical use in photoprotection against UV-induced DNA damage. The stability was investigated for feasibility to produce hydrogels containing cationic nanocapsules of the flavonoid DMY (NC-DMY) for 90 days under three different storage conditions (4 ± 2 °C, 25 ± 2 °C, and 40 ± 2 °C), as well as evaluation of skin permeation and its cytotoxicity in skin cell lines. The physicochemical and rheological characteristics were maintained during the analysis period under the different aforementioned conditions. However, at 25 °C and 40 °C, the formulations indicated yellowish coloration and DMY content reduction. Therefore, the ideal storage condition of 4 °C was adopted. DMY remained in the stratum corneum and the uppermost layers of the skin. Regarding safety, all formulations demonstrated to be safe for topical application. NC-DMY exhibited a 50% Solar Protection Factor (SPF-DNA) against DNA damage caused by UVB radiation and demonstrated 99.9% protection against DNA lesion induction. These findings establish a promising formulation containing nanoencapsulated DMY flavonoids with a photoprotective and antioxidant potential of eliminating reactive oxygen species formed by solar radiation.

Atrial fibrillation; Implantable cardioverter defibrillator; Inappropriate shock Fibrilación auricular; Desfibrilador cardioversor implantable; Shock inapropiado Fibril·lació auricular; Desfibril·lador cardioversor implantable; Xoc inadequat An implantable cardioverter defibrillator (ICD) lead dislodgement into the right atrium is a dangerous situation, particularly in patients in atrial fibrillation because atrial fibrillation can be sensed as ventricular fibrillation and true ventricular fibrillation induced with an inappropriate shock. In the presence of shocks, ICD interrogation should be performed as soon as possible.

BACKGROUND: Electrophysiological study (EPS) is indicated in patients with syncope and bundle branch block (BBB). Data about predictors of positive EPS in these patients is scarce. OBJECTIVE: To assess clinical and electrocardiographic (ECG) predictors of positive EPS in patients with syncope and BBB. METHODS: Observational single‐center study that included all consecutive patients with syncope and BBB that underwent EPS from January 2011 to June 2017. Results of EPS were considered positive according to current ESC syncope guidelines. RESULTS: During study period, 271 patients were included (64.9% male, age: 73.9 ± 12.2 years, number of syncopal episodes: 2.4 ± 2.5, LVEF: 56.1 ± 9.9%). Type of BBB: RBBB + LAFB/LPFB in 39.8%, isolated LBBB in 38.7% and isolated RBBB in 18.5% of the patients. Duration of QRS and PR interval were 141.9 ± 16.7 and 182.8 ± 52.2 milliseconds. EPS was positive in 41.7% of the patients. In multivariate analysis, conduction disturbance pattern and long PR interval (OR 8.6; 2.9‐25; P

Background: The implantable loop recorder (ILR) is a useful tool for diagnosis of syncope or palpitations. Its easy use and safety have extended its use to secondary hospitals (those without an Electrophysiology Lab). The aim of the study was to compare results between secondary and tertiary hospitals. Methods: National prospective and multicenter registry of patients with an ILR inserted for clinical reasons. Data were collected in an online database. The follow-up ended when the first diagnostic clinical event occurred, or 1 year after implantation. Data were analyzed according to the center of reference; hospitals with Electrophysiology Lab were considered Tertiary Hospi­tals, while those hospitals without a lab were considered Secondary Hospitals. Results: Seven hundred and forty-three patients (413 [55.6%] men; 65 ± 16 year-old): 655 (88.2%) from Tertiary Centers (TC) and 88 (11.8%) from Secondary Centers (SC). No differences in clinical characteristics between both groups were found. The electrophysi­ologic study and the tilt table test were conducted more frequently in Tertiary Centers. Fol­low-up was conducted for 680 (91.5%) patients: 91% in TC and 94% in SC. There was a higher rate of final diagnosis among SC patients (55.4% vs. 30.8%; p < 0.001). Tertiary Hospital patients showed a trend towards a higher rate of neurally mediated events (20% vs. 4%), while bradyarrhythmias were more frequent in SC (74% vs. 60%; p = 0.055). The rate of deaths and adverse events was similar in both populations. Conclusions: Patients with an ILR in SC and TC have differences in terms of the use of complementary tests, but not in clinical characteristics. There was a higher rate of diagnosis in Secondary Hospital patients.

BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0).INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 (-) (9); odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 (-) (9); OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

Defining the environmental context in which genes enhance disease susceptibility can provide insight into the pathogenesis of complex disorders. We report that the intra-uterine environment modulates the association of schizophrenia with genomic risk (in this study, genome-wide association study–derived polygenic risk scores (PRSs)). In independent samples from the United States, Italy, and Germany, the liability of schizophrenia explained by PRS is more than five times greater in the presence of early-life complications (ELCs) compared with their absence. Patients with ELC histories have significantly higher PRS than patients without ELC histories, which is confirmed in additional samples from Germany and Japan. The gene set composed of schizophrenia loci that interact with ELCs is highly expressed in placenta, is differentially expressed in placentae from complicated in comparison with normal pregnancies, and is differentially upregulated in placentae from male compared with female offspring. Pathway analyses reveal that genes driving the PRS-ELC interaction are involved in cellular stress response; genes that do not drive such interaction implicate orthogonal biological processes (for example, synaptic function). We conclude that a subset of the most significant genetic variants associated with schizophrenia converge on a developmental trajectory sensitive to events that affect the placental response to stress, which may offer insights into sex biases and primary prevention.

Purpose Differentiation between photoallergenic and phototoxic reactions induced by low molecular weight compounds represents a current problem. The use of keratinocytes as a potential tool for the detection of photoallergens as opposed to photoirritants is considered an interesting strategy for developing in vitro methods. We have previously shown that IL-18 production in the human keratinocyte cell line NCTC 2455 is a good model for the in vitro identification of contact sensitizers. The purpose of this manuscript is to summarize data obtained in the NCTC 2544 assay as an in vitro model to identify photoallergens and discriminate them from phototoxic chemicals. Methods The effect of UVA radiation (3.5 J/cm 2 ) over NCTC 2544 cells irradiated and non irradiated, and treated with increasing concentrations of various compounds including negative compounds (irritants and allergens), ibuprofen and acridine (photoirritants); ketoprofen, promethazine and chlorpromazine (photoirritants/photoallergens); benzophenone, 4-tert-butyl-4-methoxy-dibenzoylmethane, 2-ethylexyl-p-methoxycinnamate and 6-methylcumarin (photoallergens) was investigated. Twenty-four hours after exposure, cytotoxicity was evaluated by the MTT assay, while a commercially available ELISA kit was used to assess the intracellular content of IL-18. Result At no cytotoxic concentrations, allergens and photoallergens induce a dose-related increase in the production of IL-18, whereas irritants and photoirritants failed, indicating the possibility to use the NCTC 2544 assay to identify in vitro photoallergens.

Localized malignant pleural mesothelioma (LMPM) is rare and its natural history is not well known. There is not enough evidence to allow the physician to follow a clear therapeutic plan in everyday clinical practice. This case report is about a 40-year-old female who was being studied because of right scapular pain, neck swelling and shortness of breath that led to identify a mass in the right upper lobe. Because of the rapid growth of the mass, the patient presented acute severe respiratory insufficiency and hypoxaemia resulting in haemodynamic instability that required intubation, mechanical ventilation and vasoactive drug support. With no definitive histo-pathological diagnosis, the patient underwent emergency thoracotomy for en bloc resection of the right upper lobe, the second to fourth ribs and pericostal tissue extending to the paravertebral muscle. The patient had a favourable postoperative course. Routine pathological study of the resected specimen revealed a highly undifferentiated tumour with no further characterization. Electron microscopy revealed a malignant pleural mesothelioma (MPM). In view of the diagnosis, the patient received adjuvant chemo-radiotherapy. The patient remains disease-free 15 years after the operation. The LMPM needs to be differentiated from the diffuse form of MPM. While the latter can rarely be cured, the former can be eradicated with tumour resection en bloc with the involved structures and adjuvant therapy. The purpose of this case report is to draw attention to this localized form of MPM and to the fact that an emergency operation was required with no certain preoperative diagnosis because of the rapid growth of the tumour.

Introduction and objectives The seventh edition of the TNM classification, together with undeniable advantages, has limitations. The International Association for the Study of Lung Cancer (IASLC) Staging Committee has designed an international prospective study to improve this classification. A group of thoracic surgeons and pulmonologists was established in the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Oncology area, and created a registry of new lung cancer (LC) cases to participate in this project. The aim of this paper is to describe the main characteristics of the patients included. Materials and methods Prospective, observational, multicentre, multiregional data collection (epidemiological, clinical, therapeutic and, especially, anatomical extension) study, according to the IASLC protocol, to analyse its prognostic value. Results Two thousand, four hundred and nineteen patients (83.6% men) from 28 hospitals were included. Ninety-six percent of the men and 54% of the women were smokers or ex-smokers. Chest/abdominal computed tomography (CT) scanning was performed in over 90% and positron emission tomography (PET)/CT scanning in 51.5% of cases. Among the 1035 patients who underwent surgery, 77% had early stages ( i a to ii b), and 61.6% of those treated using other methods had stage iv . Respiratory comorbidity was higher in men (47.9% versus 21.4%). The most common histological subtype was adenocarcinoma (34%), especially in non-smoking women (69.5%). Conclusions The proportion of women and adenocarcinomas, as well as those resected at an early stage, increased among LC cases in Spain.

Progress in understanding the mechanisms of skin sensitization, provides us with the opportunity to develop in vitro tests as an alternative to in vivo sensitization testing. Keratinocytes play a key role in all phases of skin sensitization. We have recently identified interleukin-18 (IL-18) production in keratinocyte as a potentially useful endpoint for determination of contact sensitization potential of low molecular weight chemicals. The aim of the present article is to further exploit the performance of the NCTC 2544 assay. NCTC 2544 is a commercially available skin epithelial-like cell line originating from normal human skin, which posses a good expression of cytochrome P450-dependent enzymatic activities. Cells were exposed to contact allergens (2-bromo-2-bromomethyl glutaronitrile, cinnamaldehyde, citral, diethylmaleate, dinitrochlorobenzene, glyoxal, 2-mercaptobenzothiazole, nickel sulfate, 4-nitrobenzylbromide, oxazolone, penicillin G, resorcinol, tetramethylthiuram disulfide), to pre- pro-haptens (cinnamyl alcohol, eugenol, isoeugenol, p-phenylediamine), to respiratory allergens (ammonium hexachloroplatinate, diphenylmethane diisocyanate, glutaraldehyde, hexamethylenediisocyanate, maleic anhydride, trimellitic anhydride) and to irritants (benzaldehyde, cholorobenzene, diethylphtalate, hydrobenzoic acid, lactic acid, octanoic acid, phenol, salicylic acid, sodium lauryl sulphate, sulfamic acid). Cell associated IL-18 was evaluated 24 later by ELISA. At not-cytotoxic concentrations (cell viability higher of 80%, as assessed by MTT reduction assay), all contact sensitizers, including pre-pro-haptens, induced a dose-related increase in IL-18, whereas both irritants, with the exception of sulfamic acid, and respiratory allergens failed. A total of 33 chemicals were tested, with an overall accuracy of 97%. Overall, results obtained indicated that cell-associated IL-18 might provide an in vitro tool for identification and discrimination of contact vs. respiratory allergens and/or irritants.

Delivery systems with pH-responsiveness behavior are of particular interest because they could allow exploring the various pH gradients within the body, for example, between healthy tissue and tumor tissue, or between extracellular tissue and some cell compartments. Likewise, modifications in nanocarriers with polyethylene glycol (PEG) and poloxamer could be a potential approach to improve the effectiveness of cancer treatments. On these premises, we prepared pH-responsive DOX-loaded chitosan-tripolyphosphate nanoparticles (NPs), modified or not with PEG or poloxamer, and incorporating an anionic dyacyl lysine-based surfactant with sodium counterion (77KS) as a pH-sensitive adjuvant. Owing to its pH-sensitivity, the CS-NPs showed membranolytic behavior upon reducing the pH value of surrounding media to 6.6 and 5.4, which are characteristic of the endosomal compartments. The in vitro antiproliferative assays with MCF-7 and HeLa tumor cells indicated that the NPs themselves had no associated significant cytotoxicity, while DOX-loaded NPs induced higher cytotoxicity than free drug. Additionally, DOX-loaded CS-NPs displayed greater selectivity to tumor cells than to the non-tumor 3T3 fibroblasts. The feasibility of using these NPs to target tumor microenvironment was proven, as cytotoxicity against cancer cell models was higher in a mildly acidic environment. Finally, the hemocompatibility of NPs was demonstrated, indicating their suitability for intravenous administration. Altogether, the results suggest that the combination of endosomal acidity with the potential endosomolytic capability of these pH-responsive nanocarriers could increase the intracellular delivery of DOX and, thus, might enhance its antineoplastic efficacy.

The term inherited cardiovascular disease encompasses a group of cardiovascular diseases (cardiomyopathies, channelopathies, certain aortic diseases, and other syndromes) with a number of common characteristics: they have a genetic basis, a familial presentation, a heterogeneous clinical course, and, finally, can all be associated with sudden cardiac death. The present document summarizes some important concepts related to recent advances in sequencing techniques and understanding of the genetic bases of these diseases. We propose diagnostic algorithms and clinical practice recommendations and discuss controversial aspects of current clinical interest. We highlight the role of multidisciplinary referral units in the diagnosis and treatment of these conditions.

A novel series of indolocarbazoles were synthesized and their antiproliferative activity against HUVEC, LoVo, DLD-1 and ST-486 cell lines, was investigated. Those staurosporine analogs in which a substituted dimethylaminoalkoxy chain was attached to the indolic nitrogen showed interesting activity and selectivity with respect to HUVEC proliferation. The effect on capillary tube formation in 3-dimensional matrigel matrix was studied using the most active compounds. Evaluation of their in vivo anti-angiogenic activity in a murine Lewis lung cancer model was also analyzed.

Objective: To evaluate the accuracy of repeat mediastinoscopy (reMS) in all its indications, and to analyse survival in the group of patients who underwent induction chemotherapy or chemoradiotherapy for pathologically proven stage III-N2 non-small-cell lung cancer (NSCLC). Methods: From July 1992 to February 2009, 96 patients (87 men; median age: 61.3 years), underwent 101 reMSs (five patients required a second reMS) for the following indications: restaging after induction therapy for pathologically proven N2 disease (84 cases), inadequate first mediastinoscopy (five), metachronous second primary (six) and recurrent lung cancer (six). Patients with N2-NSCLC, who had received induction therapy and had positive reMS, underwent definitive chemotherapy or chemoradiotherapy. Patients in whom reMS was negative underwent thoracotomy for lung resection and systematic nodal dissection (SND). SND was considered the gold standard to compare the negative results of reMS. Pathologic findings were reviewed and staging values were calculated using the standard formulas. Follow-up data were completed in January 2010, and survival analysis was performed by the Kaplan—Meier method.Results:InthegroupofreMSforrestagingafterinductiontherapy,thestagingvalues were:sensitivity0.74,specificity1,positivepredictivevalue1,negativepredictivevalue0.79anddiagnosticaccuracy0.87.Wealsodeterminedthe diagnostic value of this technique according to the type of induction treatment. In terms of accuracy, no statistically significant differences were found.Mediansurvival timeinpatientswithtruenegativereMSwas51.5months(95%confidenceinterval(CI) 0—112), and inthe combinedgroup of patients with positive and false-negative reMS, median survival time was 11 months (95% CI 7.6—14.1) ( p = 0.0001). In the group of miscellaneous indications,allstagingvalueswere1.Conclusion:ReMSisfeasibleinalltheindicationsdescribed.Afterinductiontherapy,itisausefulprocedureto selectpatientsforlungresectionwithhighaccuracy,independentlyoftheinductiontreatmentusedortheintensityofthefirstmediastinoscopy.The persistence of lymph node involvement after induction therapy has a poor prognosis. Therefore, techniques providing cytohistological evidence of nodal downstaging are advisable to avoid unnecessary thoracotomies. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Several European Union legislations request the use of in vitro methods for toxicological evaluations, including sensitization, in order to increase consumer safety but also to reduce the use of animals. The EU project SENS-IT-IV addresses the need of developing predictive in vitro tests to assess contact and respiratory hypersensitivity reactions. In this context, we have recently reported the possibility to use IL-18 production in the human keratinocyte cell line NCTC 2544 to discriminate contact sensitizer from irritants and low molecular weight respiratory allergens. The aims of the present study were to further develop this assay in order to optimize experimental conditions; to develop a 96-well plate format to establish a high throughput assay; to test the performance of other available keratinocyte cell lines, and to understand the signal transduction pathway involved in p-phenylenediamine (PPD)-induced IL-18 production. If cells reach confluence at the moment of treatment, the ability to identify contact allergens is lost; therefore a careful check for the optimal cell density using PPD as reference contact allergen is critical. In our hands, a cell density of 1-2.5 × 10(5)cells/ml gave optimal stimulation. In order to develop a high throughput test, cells seeded in 96-well plate were exposed to contact allergens (2,4-dinitrochlorobenzene, p-phenylenediamine, isoeugenol, cinnamaldehyde, tetramethylthiuram disulfite, resorcinol, cinnamic alcohol and eugenol), irritants (phenol, sodium laurel sulphate, lactic acid and salicylic acid) and respiratory allergens (hexachloroplatinate, diphenylmethane diisocyanate, trimellitic anhydride). A selective increase in total (intracellular plus released) IL-18 was observed 24h later in cells treated with contact allergens, whereas no changes were observed following treatment with respiratory allergens and irritants, confirming previous results obtained in a 24-well format assay. A selective induction of IL-18 was also obtained testing with PPD other keratinocyte cell lines, namely HPKII and HaCaT, with the HPKII showing the highest stimulation index. Regarding the signal transduction pathway, we could demonstrate using selective inhibitors a role for oxidative stress, NF-κB and p38 MAPK activation in PPD-induced IL-18 production. In conclusion, results obtained suggest that the production of IL-18 represents a promising endpoint for the screening of potential contact allergens. The assay can be performed in a 96-well plate format, different keratinocyte cell lines can be used, and a role for oxidative stress in contact allergen-induced IL-18 was demonstrated.

Natural or designed peptide ligands rarely bind to cognate receptors in their most stable conformation when in solution. The receptor, through reciprocal induced fitting, applies pressure on the conformational ensemble of the peptide to select its complementary conformation. Given the flexible nature of the peptides’ modular architecture, a bioactive sequence must often be primed for recognition of its target to achieve high binding affinity or specificity. For rational peptide design, cyclization or structure-inducing residues have been successfully used to accomplish ligand preorganization. However, deconvolution of the averaged NMR spectra of strained peptides or other macrocycles had shown that the bound-state conformations are poorly populated in the free uncomplexed state. In small cyclic peptides, the stereochemistry of the backbone, rather than interactions with or among side chains, determines the conformational ensemble by establishing a defined pattern of local torsional preferences. Intramolecular H bonds act on the equilibrium distribution of the conformational ensemble and favor specific conformations. Thus, we envisioned amide-to-ester substitution or “Ester Scan” as an interesting modification for the peptide backbone, which influences the conformational ensemble as well as its equilibrium distribution; this influence is achieved through modulation of the backbone torsional preferences and H-bonding pattern, respectively. As a model we choose cilengitide (CIL), which is an ArgGly-Asp (RGD) peptide of sequence cyclo[RGDfNMeV] (see Scheme 1), with well-characterized biological and conformational properties. CIL displays nanomolar inhibition of vitronectin binding to the isolated avb3 and avb5 integrin receptors, and it blocks integrin-dependent adhesion of tumor and endothelial cells to immobilized extracellular matrix (ECM) proteins and reduces angiogenesis and tumor growth in vivo. Modulation of the internal H-bond pattern of nonmethylated CIL precursors—achieved by changing the flexibility or the chirality of the backbone—was found to influence the antagonist activity on the vitronectin (VN) and fibrinogen (FB) receptors, and has been proposed to control laminin P1 vs. vitronectin receptor specificity. We synthesized all five depsi-analogues of the depsipeptide CIL (D1–D5) by stepwise assembling of the linear precursors on 2-CTC resin (Fmoc/tBu strategy) and cyclization in solution. For the introduction of the a-hydroxy acid residues onto the growing peptide chain, their HFA-activated/protected derivatives were used (Scheme 1). For the acylation of the free hydroxy group, DIPDCI/DMAP-activation was used. For conventional peptide cyclization, the optimal site for macrocycle formation is between the Gly (acting as the C terminus) and Asp (acting as the N terminus) residues because Gly cannot epimerize. This strategy was used for the synthesis of parent CIL, D1, and D2 depsipeptides with PyBOP/HOAt. The macrolactonization required for the preparation of D3 was successful with MSNT activation and NMI as the base. For the depsipeptides D4 and D5, certain particularities of the ester bond had to be taken into account. Our attempts to synthesize the linear precursor of D4 (OGly analogue) starting from OGly as the C terminus, resulted in low yields, and was likely because of cleavage of the ester bond that was mediated by base during repeated treatment with piperidine. Therefore, NMeVal was chosen as the C terminus. For the preparation of D5, the cyclization was performed at the (apparently) less attractive position between (d)Phe and NMeVal. Macrolactamization at less hindered sites was impeded by intramolecular nucleophilic attack on the ester bond, which occurred during peptide chain elongation, and eliminated the (D)Phe–NMeVal couple as dioxopiperazine. Given the increased steric demand of the N-terminal NMeVal, we chose the more reactive PyAOP as the coupling reagent and HOAt as the additive. After cleavage from the solid support, all linear peptide and depsipeptide precursors were obtained in over 85% yield. Head-to-tail cyclization was performed in solution and gave good yields in all cases and, finally, the protecting groups on the side chains were removed using [Pd(PPh3)4]/phenylsilane [*] T. Cupido, Dr. J. Spengler, Dr. J. Ruiz-Rodriguez, Prof. F. Albericio Institute for Research in Biomedicine (IRB), Barcelona Science Park (PCB) and CIBER-BBN Networking Centre on Bioengineering, Biomaterials and Nanomedicine PCB Baldiri Reixac 10, 08028 Barcelona (Spain) Fax: (+34)93-403-7126 E-mail: tommaso.cupido@irbbarcelona.org albericio@irbbarcelona.org

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.Methods: In view of these findings, we examined the role ofβ3in pancreatic cancer by generating two stableβ3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.Results: Transduction ofβ3selectively augmented the functional membraneαvβ3integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected inβ3-overexpressing cells. Moreover, tumors expressingβ3displayed reduced growth. Interestingly, treatment of mice with anαv-blocking antibody inhibited the growth ofβ3-expressing tumors to a higher extent.Conclusion: Our results collectively support the hypothesis thatαvβ3integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.

Extensive efforts have been made, recently, to find surfactants with lower irritancy potential than those presently commercially employed in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of novel mono and diacylglycerol amino acid-based surfactants (glutamic acid, or arginine) were evaluated. All tested surfactants showed a clear concentration–response relationship to two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, demonstrated by and decrease of NR uptake. Concentrations resulting in 50% inhibition of NR uptake (IC 50 ) range from 30 to 300 μg mL −1 . The potential phototoxicity which could result in irritant products, was determined by modulated cytotoxicity via the resazurin reduction to resorufin and neutral red uptake (NRU) endpoints. Surfactants with two chains showed, in general, less cytotoxic but higher phototoxic effect than surfactants with only one chain.

Purpose Quantification of eye irritancy has been a problem for both the consumer product industry and ophthalmic researchers because of the need to predict the toxic potential of preparations that may come into contact with the ocular surface. The Draize rabbit eye test has been used for 60 years in attempts to predict human ocular irritancy based on topical instillation of the potential irritant and subjective scoring of ocular inflammation by direct visualization of the rabbit eye. The inadequacies of the Draize test have led to efforts in several laboratories to develop alternatives. Methods We propose an alternative to the Draize eye irritation test, using human hemoglobin rather than bovine hemoglobin and studying the protein denaturation induced by potential irritants. Among the factors that affect eye irritation, protein denaturation has been reported as one of the most important factors that can result in corneal opacity. Human protein denaturation was measured as indicative of eye irritation. Results We studied different known irritant and non-irritant compounds to establish the predictability of the method. The compounds considered as irritants in vivo had the greatest effect in terms of decreased human hemoglobin absorbance. Conclusions The proposed method is able to easily differentiate between irritant and non-irritants products in an easy manner. The method is easy, rapid, economical, and provides enough information about the potential eye irritant action of different surfactants.

Objective: To evaluate the technical feasibility and the sensitivity, specificity and accuracy of extended cervical mediastinoscopy (ECM) in the staging of bronchogenic carcinoma (BC) of the left lung. Methods: From 1998 to 2003, 89 patients underwent routine ECM for staging of BC of the left lung. In 2004, positron emission tomography (PET) was included in our staging protocol and ECM was reserved for those with positive mediastinal or hilar PET images, large lymph nodes on computed tomography (CT) scan or central tumours. From 2004 to 2007 we performed selective ECM in 67 patients. ECM was considered positive when metastatic nodes or tumour involvement directly in the subaortic or para-aortic regions was confirmed pathologically. One hundred and forty-three patients with negative ECM underwent subsequent thoracotomy for tumour resection and systematic nodal dissection. Pathological findings were reviewed and staging values were calculated. Results: One hundred and fifty-six patients underwent ECM (89 routine and 67 selective). In 13, ECM was positive and thoracotomy was contraindicated. The rest of the patients were operated. We performed 88 lobectomies, 34 pneumonectomies, 6 wedge resections, 13 exploratory thoracotomies and 2 parasternal mediastinotomies. Lymphadenectomy specimens showed tumour involvement of subaortic lymph nodes in 8 patients. Complication rate was 2%: two cases of mediastinitis, one ventricular fibrillation, and one superficial surgical wound infection. Sensitivity, specificity, positive predictivevalue,negativepredictivevalueandaccuracyofroutine/selectiveECMwere:0.45/0.75,1/1,1/1,0.94/0.95,0.94/0.95,respectively. Conclusion:ECMis a feasiblestagingtechnique thatallowsruling outsubaorticandpara-aorticnodaldiseasewith highnegativepredictivevalue, accuracyandsensitivity.ItsindicationbasedontheCTandPETfindingsseemsmoreadvisablethatitsroutineusetostagebronchogeniccarcinoma of the left lung. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

The aim of this work was to evaluate possible cytotoxic effects of topical creams and lotions produced with Buriti oil and commercial surfactants on human keratinocytes HaCat and 3T3 embryonic mouse fibroblast cultures. We also aimed to assess the cytotoxicity of the surfactants used to produce the emulsions. The neutral red release (NRR) assay was performed as an in vitro method to evaluate the cytotoxicity of the emulsions in HaCat and 3T3 cell lines and predict potential skin irritation. The Buriti oil emulsions presented low cytotoxicity to the cells at high concentrations and the addition of Vitamin E increased cell viability. Among the surfactant tested, Unitol CE 200F proved to be the most cytotoxic, presenting an IC(50) significantly lower than the others. Emulsions formulated with Buriti oil and commercial surfactants could be non irritant to the skin due to their low cytotoxicity, especially when enhanced with vitamin E. When emulsified with Buriti oil, water and Brij 72, Unitol CE 200F showed less cytotoxic effects than when tested alone.

Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were highly active as free radical scavengers against ABTS, DPPH (hydrogen donation and electron transfer), and HNTTM (electron transfer). They were also able to reduce the newly introduced TNPTM radical, meaning that they included some highly reactive components. Witch hazel phenolics protected red blood cells from free radical-induced hemolysis and were mildly cytotoxic to 3T3 fibroblasts and HaCat keratinocytes. They also inhibited the proliferation of tumoral SK-Mel 28 melanoma cells at lower concentrations than grape and pine procyanidins. The high content in pyrogallol moieties may be behind the effect of witch hazel phenolics on skin cells. Because the most cytotoxic and antiproliferative mixtures were also the most efficient as electron transfer agents, we hypothesize that the final putative antioxidant effect of polyphenols may be in part attributed to the stimulation of defense systems by mild prooxidant challenges provided by reactive oxygen species generated through redox cycling.

Syncope is defined as the transient loss of consciousness with spontaneous recovery, as a result of cerebral hypoperfusion. It is a very common clinical entity.1 Although it is difficult to establish the prevalence and incidence of syncopal episodes, recent data indicate that 9-35% of the Spanish population present some syncopal episode in their lifetime.2,3 There are a variety of causes which may trigger a syncopal episode.1 The most common is the neurally mediated response, in which a distinction should be made between vasovagal syncope, situational syncope, and syncope resulting from carotid sinus hypersensitivity. The second major cause is arrhythmia, whether this be bradyarrhythmia or tachyarrhythmia, which are common in patients with abnormal electrocardiograms (ECG) or different grades of structural heart disease. Syncope as a result of orthostatic hypotension is less common and is usually secondary to dysautonomia or the administration of drugs. Occasionally, syncope can be a clinical manifestation of different acute cardiopulmonary conditions, such as pulmonary embolism, myocardial infarction, or cardiac tamponade. On rare occasions it may be caused by subclavian steal syndrome. The severity and clinical impact of syncopal episodes are determined not only by their etiology, but also by other circumstances, such as how the episodes present themselves, the recurrence rate or the patient’s professional circumstances. Occasional syncopal episodes of a vasovagal etiology, with recognisable triggers and prodromes, therefore constitute a benign clinical episode Management of Patients With Syncope: From Guidelines to Clinical Practice

8 pages, 3 figures.-- PMID: 17293064 [PubMed].-- Printed version published on Mar 8, 2007., Surfactants have the special ability to interact with the lipid bilayer of cell membranes. The red blood cell is one of the most used cellular membrane models to study the mechanisms underlying surfactant-induced osmotic cell resistance. To increase our knowledge regarding the mechanisms of surfactant membrane interaction, we studied the action of five lysine-derivative anionic and three arginine-derivative cationic amino acid-based surfactants on hypotonic hemolysis. Results showed two different antihemolytic behaviors among amino acid-based surfactants, both related to the maximal protective concentration. How the physico-chemical properties and structure of these compounds determine the protection against hypotonic hemolysis is discussed in detail. We found a good correlation between the CMC and the concentrations resulting in maximum protection against hypotonic hemolysis for the cationic surfactants, but no correlation for the anionic surfactants. In the case of lysine derivative surfactants, which only differ in their counterions, the counterion is implicated in the differences in the antihemolytic potency and the hemolytic activities of this., This research was supported by the Project PPQ- 2003-01834 from MCTE (Spain). Verónica Martínez and Lourdes Sánchez hold doctoral grants from Universitat de Barcelona (Spain) and Unidad Asociada-CSIC (Spain), respectively. The authors are grateful to Robin Rycroft for linguistic assistance.

The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy.