Evaluación del cribado y la efectividad de una intervención breve en bebedores de riesgo atendidos en consultas de atención primaria

ObjetivosEvaluar el cribado y la efectividad de una intervención breve antialcohólica, el grado de aceptación y la evolución de los parámetros biológicos asociados con el consumo de alcohol tras la intervención.DiseñoEstudio prospectivo longitudinal de intervención de 1 año de duración.EmplazamientoCinco consultas de atención primaria urbanas.ParticipantesDe una muestra aleatoria de 681 sujetos de ambos sexos y de edad de 18-65 años, se seleccionó a 78 bebedores de riesgo. Los que cumplían criterios de exclusión (n=10), no aceptaban participar (n=24) y presentaban sospecha de síndrome de dependencia alcohólica (n=11) no participaron en el estudio.IntervencionesSe ofrecía un breve consejo antialcohólico apoyado con soporte escrito, y se realizaba un seguimiento a los 2 y 12 meses mediante la cuantificación del consumo de alcohol y un control analítico.Mediciones principalesSe estimó la prevalencia de bebedores de riesgo, el grado de aceptación a participar en el estudio, la disminución del consumo de alcohol y de bebedores de riesgo a los 2 y 12 meses, y la evolución de los parámetros analíticos tras la intervención.ResultadosLa prevalencia de bebedores de riesgo fue del 11,5% (intervalo de confianza [IC] del 95%, 8,3-14,7%). El grado de aceptación a participar en el estudio fue del 64,7%. Se observó un decremento significativo (p<0,05) en el consumo de alcohol a los 2 y 12 meses, así como una disminución de los bebedores de riesgo, que a los 2 meses fue del 57,6% (IC del 95%, 50,3-64,9%; p=0,01) y a los 12 meses del 42,4% (IC del 95%, 35,9-48,9%; p=0,003). Asimismo, se produjeron disminuciones significativas en las concentraciones de GGT, VCM, colesterol y triglicéridos.ConclusionesSe observa una baja prevalencia de bebedores de riesgo sin sospecha de síndrome de dependencia alcohólica en nuestro medio, así como una elevada efectividad del consejo breve antialcohol y del grado de aceptación a participar en el estudio. Se apreció una disminución de las concentraciones de GGT, VCM, colesterol y triglicéridos tras la intervención.AimsTo evaluate the screening, the effectiveness of an antialcoholic brief intervention for risk drinkers, the acceptation level to participate in this study, and the analytical parameters evolution associated to the alcohol consumption after of the intervention.DesignLongitudinal prospective intervention study of 1 year of duration.Setting5 urban primary care physician's practices.ParticipantsOf an aleatory pattern of 681 patients, men and women of 18-65 years old, were selected 78 risk drinkers. Patients with exclusion criteria (n=10), didn’t wanted to participate (n=24) and had suspicion of alcoholic dependence syndrome (ADS) (n=11), didn’t participated in this intervention.InterventionsWere offered antialcoholic brief counselling with written supporter and were followed with alcohol consumption rate and analytical control at 2 and 12 months.Main measuresWas estimated the prevalence of risk drinkers, the acceptation level to participate in this study, alcohol consumption and risk drinkers decreased at 2 and 12 months, analytical parameters evolution after of the intervention.ResultsPrevalence of risk drinkers: 11.5% (95% confidence interval [CI], 8.3%-14.7%). Acceptation level to participate in this study: 64.7%. Significative alcohol consumption decreased at 2 and 12 months (P<.05). Risk drinkers decreased: at 2 months were 57.6% (95% CI, 50.3%-64.9%; P=.01) and at 12 months were 42.4% (95% CI; 35.9%-48.9%) (P=.003). GGT, MCV, cholesterol, and triglycerides significative decreased.ConclusionsLow prevalence of risk drinkers without suspicion of ADS in our setting; high effectiveness of antialcoholic brief counselling and high acceptation level to participate in this study; reduction of the GGT, MCV, cholesterol, and triglycerides after of the intervention

Single-cultivar extra virgin olive oil classification using a potentiometric electronic tongue

Label authentication of monovarietal extra virgin olive oils is of great importance. A novel approach based on a potentiometric electronic tongue is proposed to classify oils obtained from single olive cultivars (Portuguese cvs. Cobrançosa, Madural, Verdeal Transmontana; Spanish cvs. Arbequina, Hojiblanca, Picual). A meta-heuristic simulated annealing algorithm was applied to select the most informative sets of sensors to establish predictive linear discriminant models. Olive oils were correctly classified according to olive cultivar (sensitivities greater than 97%) and each Spanish olive oil was satisfactorily discriminated from the Portuguese ones with the exception of cv. Arbequina (sensitivities from 61% to 98%). Also, the discriminant ability was related to the polar compounds contents of olive oils and so, indirectly, with organoleptic properties like bitterness, astringency or pungency. Therefore the proposed E-tongue can be foreseen as a useful auxiliary tool for trained sensory panels for the classification of monovarietal extra virgin olive oils.This work was co-financed by FCT and FEDER under Program COMPETE (Project PEst-C/EQB/LA0020/2013)

Contrasting anticancer activity of half-sandwich iridium(III) complexes bearing functionally diverse 2-phenylpyridine ligands

We report the synthesis, characterization, and antiproliferative activity of 15 iridium(III) half-sandwich complexes of the type [(η5-Cp*)Ir(2-(R′-phenyl)-R-pyridine)Cl] bearing either an electron-donating (−OH, −CH2OH, −CH3) or electron-withdrawing (−F, −CHO, −NO2) group at various positions on the 2-phenylpyridine (2-PhPy) chelating ligand giving rise to six sets of structural isomers. The X-ray crystal structures of [(η5-Cp*)Ir(2-(2′-fluorophenyl)pyridine)Cl] (1) and [(η5-Cp*)Ir(2-(4′-fluorophenyl)pyridine)Cl] (2) exhibit the expected “piano-stool” configuration. DFT calculations showed that substituents caused only localized effects on the electrostatic potential surface of the chelating 2-PhPy ligand of the complexes. Hydrolysis of all complexes is rapid, but readily reversed by addition of NaCl. The complexes show preferential binding to 9-ethylguanine over 9-methyladenine and are active catalysts for the oxidation of NADH to NAD+. Antiproliferative activity experiments in A2780 ovarian, MCF-7 breast, A549 lung, and HCT116 colon cancer cell lines showed IC50 values ranging from 1 to 89 μM, with the most potent complex, [(η5-Cp*)Ir(2-(2′-methylphenyl)pyridine)Cl] (13) (A2780 IC50 = 1.18 μM), being 10× more active than the parent, [(η5-Cp*)Ir(2-phenylpyridine)Cl], and 2× more active than [(η5-CpxPh)Ir(2-phenylpyridine)Cl]. Intriguingly, contrasting biological activities are observed between structural isomers despite exhibiting similar chemical reactivity. For pairs of structural isomers both the nature and position of the functional group can affect the hydrophobicity of the complex. An increase in hydrophobicity resulted in enhanced cellular-iridium accumulation in A2780 ovarian cells, which generally gave rise to an increase in potency. The structural isomers [(η5-Cp*)Ir(2-(4′-fluorophenyl)pyridine)Cl] (2) and [(η5-Cp*)Ir(2-phenyl-5-fluoropyridine)Cl] (4) preferentially localized in the cytosol > membrane and particulate > nucleus > cytoskeleton. This work highlights the strong dependence of biological behavior on the nature and position of the substituent on the chelating ligand and shows how this class of organometallic anticancer complexes can be fine-tuned to increase their potency without using extended cyclopentadienyl systems

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides

Monovarietal extra-virgin olive oil classification: a fusion of human sensory attributes and an electronic tongue

Olive oil quality grading is traditionally assessed by human sensory evaluation of positive and negative attributes (olfactory, gustatory, and final olfactorygustatory sensations). However, it is not guaranteed that trained panelist can correctly classify monovarietal extra-virgin olive oils according to olive cultivar. In this work, the potential application of human (sensory panelists) and artificial (electronic tongue) sensory evaluation of olive oils was studied aiming to discriminate eight single-cultivar extra-virgin olive oils. Linear discriminant, partial least square discriminant, and sparse partial least square discriminant analyses were evaluated. The best predictive classification was obtained using linear discriminant analysis with simulated annealing selection algorithm. A low-level data fusion approach (18 electronic tongue signals and nine sensory attributes) enabled 100 % leave-one-out cross-validation correct classification, improving the discrimination capability of the individual use of sensor profiles or sensory attributes (70 and 57 % leave-one-out correct classifications, respectively). So, human sensory evaluation and electronic tongue analysis may be used as complementary tools allowing successful monovarietal olive oil discrimination.This work was co-financed by FCT/MEC and FEDER under Program PT2020 (Project UID/EQU/50020/2013); by Fundacao para a Ciencia e Tecnologia under the strategic funding of UID/BIO/04469/2013 unit; and by Project POCTEP through Project RED/AGROTEC-Experimentation network and transfer for development of agricultural and agro industrial sectors between Spain and Portugal

Efectos psicosociales y culturales del desplazamiento

El libro presenta una aproximación a una lectura psicosocial de los efectos del conflicto armado, con ello queremos aportar elementos teóricos y metodológicos a los profesionales interesados, para que puedan intervenir, no sólo en lo que tiene que ver con el sufrimiento emocional de quienes directa o indirectamente viven esta tragedia, sino para que logren incidir en la construcción de alternativas colectivas para prevenir y enfrentar las múltiples consecuencias que genera el desplazamiento forzoso. / Contenido. Preliminares; Capítulo 1 - Impactos psicosociales del desplazamiento y estrategias de intervención; Capítulo 2 - Impactos sociales y culturales del desplazamiento. Capítulo 3 - Impactos del desplazamiento: una mirada de género y de generación; Capítulo 4 - Propuestas y experiencias de atención

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1