Determinantes del tratamiento de las queratosis actínicas por médicos de atención primaria / Actinic Keratosis and Primary Care Physicians: Factors Affecting the Decision to Treat or Not

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Tuning the charge flow between Marcus regimes in an organic thin-film device.

Marcus's theory of electron transfer, initially formulated six decades ago for redox reactions in solution, is now of great importance for very diverse scientific communities. The molecular scale tunability of electronic properties renders organic semiconductor materials in principle an ideal platform to test this theory. However, the demonstration of charge transfer in different Marcus regions requires a precise control over the driving force acting on the charge carriers. Here, we make use of a three-terminal hot-electron molecular transistor, which lets us access unconventional transport regimes. Thanks to the control of the injection energy of hot carriers in the molecular thin film we induce an effective negative differential resistance state that is a direct consequence of the Marcus Inverted Region.

Spin doping using transition metal phthalocyanine molecules.

Molecular spins have become key enablers for exploring magnetic interactions, quantum information processes and many-body effects in metals. Metal-organic molecules, in particular, let the spin state of the core metal ion to be modified according to its organic environment, allowing localized magnetic moments to emerge as functional entities with radically different properties from its simple atomic counterparts. Here, using and preserving the integrity of transition metal phthalocyanine high-spin complexes, we demonstrate the magnetic doping of gold thin films, effectively creating a new ground state. We demonstrate it by electrical transport measurements that are sensitive to the scattering of itinerant electrons with magnetic impurities, such as Kondo effect and weak antilocalization. Our work expands in a simple and powerful way the classes of materials that can be used as magnetic dopants, opening a new channel to couple the wide range of molecular properties with spin phenomena at a functional scale.

Estudio piloto sobre el estrés y la resiliencia familiar en recién nacidos prematuros / Pilot study on stress and resilience in families with premature newborns

INTRODUCCIÓN: La prematuridad se acompaña de patología severa, estancias prolongadas en el hospital e incertidumbre acerca del futuro de los pacientes. Estas circunstancias suponen un estrés que puede afectar al funcionamiento de la familia. El objetivo de este trabajo ha sido estudiar los factores de riesgo y de protección del funcionamiento familiar en prematuros comparados con neonatos sanos a término. Población y métodos: Se reclutó a prematuros que cursaron el periodo neonatal con y sin patología (n=40) a los 24 meses de edad posconcepcional y un grupo control de nacidos a término sanos (n=31) según datos de la historia clínica. El progenitor cuidador habitual respondió al Inventario de Factores de Protección Familiar y Escala de Estrés Parental. Los resultados se compararon mediante test de Student, análisis de variancia unidireccional y test de Tukey. RESULTADOS: Los padres del grupo control obtuvieron puntuaciones más elevadas que los de los prematuros en todos los parámetros estudiados. Los padres de prematuros sin patología se diferenciaron de los controles en 2 factores de resiliencia familiar: experiencias positivas y experiencias de compensación y en estrés, mientras que los padres de niños prematuros con patología percibieron significativamente menor resiliencia familiar y más estrés por la crianza de sus hijos. CONCLUSIONES: La prematuridad es un factor de riesgo para el funcionamiento familiar, ya que ocasiona un alto grado de estrés parental y dificulta el desarrollo de factores de protección como es la resiliencia

INTRODUCTION: Prematurity is associated with severe clinical conditions, long hospital stays, and uncertainty about patient outcomes. These circumstances lead to a stressful situation that may affect family functioning. The aim of this study was to study risk and protection factors affecting family functioning in preterm as compared to healthy term infants. Population and methods: Preterm infants with and without pathological conditions (n=40) were recruited at 24 months post-conception age, together with a control group of healthy term newborn infants (n=31). Parents or usual caregivers responded to the Inventory of Family Protection Factors and Parental Stress scales. The results were compared using the Student t test, unidirectional analysis of variance and the Tukey test. RESULTS: Parents of the control group attained higher scores than those of the preterm group for all the items studied; however, parents of preterm infants with pathological conditions perceived significantly less family resilience and more stress related to the upbringing of their child. CONCLUSIONS: Prematurity itself is a risk factor for family dysfunction because it causes an elevated degree of parental stress and difficulties in the development of protection factors such as resilience

[Pilot study on stress and resilience in families with premature newborns]. / Estudio piloto sobre el estrés y la resiliencia familiar en recién nacidos prematuros.

INTRODUCTION: Prematurity is associated with severe clinical conditions, long hospital stays, and uncertainty about patient outcomes. These circumstances lead to a stressful situation that may affect family functioning. The aim of this study was to study risk and protection factors affecting family functioning in preterm as compared to healthy term infants. POPULATION AND METHODS: Preterm infants with and without pathological conditions (n=40) were recruited at 24 months post-conception age, together with a control group of healthy term newborn infants (n=31). Parents or usual caregivers responded to the Inventory of Family Protection Factors and Parental Stress scales. The results were compared using the Student t test, unidirectional analysis of variance and the Tukey test. RESULTS: Parents of the control group attained higher scores than those of the preterm group for all the items studied; however, parents of preterm infants with pathological conditions perceived significantly less family resilience and more stress related to the upbringing of their child. CONCLUSIONS: Prematurity itself is a risk factor for family dysfunction because it causes an elevated degree of parental stress and difficulties in the development of protection factors such as resilience.

Determination of energy level alignment at metal/molecule interfaces by in-device electrical spectroscopy.

The energetics of metal/molecular semiconductor interfaces plays a fundamental role in organic electronics, determining the performance of very diverse devices. So far, information about the energy level alignment has been most commonly gained by spectroscopy techniques that typically require experimental conditions far from the real device operation. Here we demonstrate that a simple three-terminal device allows the acquisition of spectroscopic information about the metal/molecule energy alignment in real operative condition. As a proof of principle, we employ the proposed device to measure the energy barrier height between different clean metals and C60 molecules and we recover typical results from photoemission spectroscopy. The device is designed to inject a hot electron current directly into the molecular level devoted to charge transport, disentangling the contributions of both the interface and the bulk to the device total resistance, with important implications for spintronics and low-temperature physics.

[Acetate-free on-line PHF: how to improve hyperacetatemia and haemodynamic tolerance]. / PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica.

SUMMARY BACKGROUND: The small quantity of acetate present in the dialysis fluid exposes patient's blood to an acetate concentration 30-40 times the physiological levels. This amount is even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. METHODS: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. RESULTS: Postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with postdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride postdialysis were higher and serum concentrations of bicarbonate pre and posthemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. CONCLUSIONS: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate.

PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica / No disponible

Antecedentes: la presencia de acético en el Líquido de Diálisis (LD) expone al paciente a una concentración de acetato 30-40 veces superior a la normal. Dicha exposición aumenta en técnicas de Hemodiafiltración (HDF) online. El objetivo de dicho estudio fue evaluar los cambios clínico-analíticos al usar tres técnicas de Hemodiálisis(HD) diferentes. Métodos: se reclutaron 35 pacientes en HD estable. Se dializaron tres meses con HD convencional y luego fueron aleatorizados para pasar a una técnica de PHF on-line con concentrado convencional seis meses, y después pasaron a PHF on-line sin acetato otros seis meses. El otro grupo invertía estos dos períodos. Se obtuvieron análisis de sangre y datos clínicos de HD. Resultados: las medias de los acetatos posdiálisis fueron significativamente superiores durante los períodos de tratamiento con acético respecto al período sin acetato. El porcentaje de valores patológicos de acetato posdiálisis fue significativamente superior durante los períodos de tratamiento con acético (61 respecto al 30%). Las concentraciones de cloro pos-HD fueron superiores y las de bicarbonato pre y pos-HD fueron menores durante el período sin acético. El número de hipotensiones fue significativamente inferior en el período de PHF on-line con LD estándar respecto a los otros períodos. Conclusiones: la técnica de PHF on-line sin acetato disminuye la exposición a concentraciones elevadas de acetato y consigue que la mayoría de pacientes termine la HD con una acetatemia en el rango fisiológico. La PHF on-line es un tratamiento de HDF predilucional con mejor tolerancia que la HD estándar con bicarbonato (AU)

Summary Background: the small quantity of acetate present in the dialysis fluid exposes patient’s blood to an acetate concentration 30-40 times the physiological levels. This amountis even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. Methods: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. Results: Posdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with posdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride posdialysis were higher and serum concentrations of bicarbonate pre and poshemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. Conclusions: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate (AU)

Effect of prenatal exposure to ethanol on hepatic elongation factor-2 and proteome in 21 d old rats: protective effect of folic acid.

In this article, we study the effects of ethanol intake during pregnancy and lactation on hepatic and pancreatic elongation factor-2 (EF-2) of 21 d old progeny. At the same time, the effect of ethanol on the level of other relevant hepatic proteins was determined using proteomic analysis. The results show that ethanol not only produces a general increase of protein oxidation, but also produces an important depletion of EF-2 and several other proteins. Among the hepatic proteins affected by ethanol, the concomitant supplementation with folic acid to alcoholic mother rats prevented EF-2, RhoGDI-1, ER-60 protease, and gelsolin depletion. This protective effect of folic acid may be related to its antioxidant properties and suggests that this vitamin may be useful in minimizing the effect of ethanol in the uterus and lactation exposure of the progeny.

Diagnostic value of cytokeratin fragment 19 (CYFRA 21-1) in bronchoalveolar lavage fluid in lung cancer.

The aim of this study was to evaluate the diagnostic value of a new tumour marker, cytokeratin fragment 19 (CYFRA 21-1), in bronchoalveolar lavage fluid (BALF) for the diagnosis of lung cancer. The cross-sectional study included 36 patients with lung cancer, 19 with benign lung diseases and 13 control subjects. In the group with cancer, BAL was performed in the cancer-involved lung and in the opposite lung. Results in BALF were expressed both as absolute concentrations (ng ml-1) and referred to total protein (TP) (ng mg-1 TP), and results in plasma were expressed in ng ml-1. In BALF, there was no significant different between cancer and control groups. Using the 95th percentile of levels obtained in benign lung disease in BALF (specificity 95%) as the cut-off point, the sensitivity of CYFRA 21-1 was 13%. Positive and negative predictive values (PPV and NPV) at different pretest probabilities, and positive and negative gains were obtained applying a Bayesian analysis. Results showed low positive gains for PPV (maximal increase of 22%) and almost none for NPV (negative gains < 5%). In plasma, CYFRA 21-1 provided a sensitivity of 65%. The combination of BALF and plasma tumour marker levels showed a sensitivity of 69%. Therefore, measurement of CYFRA 21-1 in BALF has poor diagnostic value in lung cancer.

Physical mapping of human insulin-like growth factor-I using specific monoclonal antibodies.

The primary structure of recombinant human (h) insulin-like growth factor-I (IGF-I) epitopes recognized by a panel of 28 monoclonal antibodies (mAbs) is characterized. Pairwise mAb epitope mapping defines eight 'epitopic clusters' (I-VIII) which cover nearly the entire solvent-exposed IGF-I surface. Monoclonal antibody reactivity with 32 overlapping synthetic peptides and with IGF-I mutants is used to associate these epitopic clusters with the probable primary IGF-I sequences recognized. Epitopic cluster I involves residues in the C-domain and the first alpha-helix of the A-domain; clusters II, V and VII involve principally the B-domain; clusters III and IV map to amino acid sequences (55-70) and (1-13) respectively; cluster VI includes the A- and B-domains; and cluster VIII involves mainly the C-terminal part of the B-domain. Data indicate that this mAb panel defines 14 distinct IGF-I epitopes. The specific inhibition of HEL 92.1.7 IGF-I-promoted proliferation by these mAbs was explored. Direct correlation between mAb affinity and inhibitory activity was observed except in the case of clusters III- and VIII-specific mAbs. Finally, the combination of epitopic cluster I and II mAbs detect 0.5-10 ng/ml hIGF-I in a sandwich immunoassay, with no IGF-II crossreactivity. These anti-IGF-I mAbs are, therefore, useful for both the inhibition of IGF-I mitogenic activity and for the quantification of this growth factor. The potential use of this mAb panel in tumor cell growth control is discussed.

Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis.

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.

Functional epitope mapping of insulin-like growth factor I (IGF-I) by anti-IGF-I monoclonal antibodies.

Based on a collection of monoclonal antibodies (mAb) against insulin-like growth factor I (IGF-I), we have defined the IGF-I epitopes involved in the interaction with IGF-binding proteins (IGFBP) and IGF-I receptors. We have also characterized the ability of these antibodies to block IGF-I-induced survival of the IL-3-dependent Ba/F3 cell line. More than 140 hybridomas secreting IGF-I-specific mAb were characterized, of which 28 were studied in detail. They display apparent affinity constants ranging from less than 10(6) to 10(10) M-1 and varying crossreactivity with IGF-II, including 2 mAb with higher affinity for IGF-II than for IGF-I. None crossreact with insulin or any other growth factor tested. Using both enzyme immunoassays and real-time biospecific interaction analysis, we have identified 8 epitopic clusters related to the primary structure of IGF-I, according to mAb reactivity to synthetic peptides, proteolytic fragments of IGF-I, and various IGF-I mutants. The mAb panel also was used to map the IGF domains implicated in the interaction with IGFBP and IGF-I receptors. An IGF-I domain has been identified that remains exposed after IGF-I binding to IGFBP-1 or to IGFBP-3, which is recognized by 6 different mAb. The mAb in this group also bind IGF-I, when complexed to the type-1 IGF receptor on the murine pro-B cell line Ba/F3, and BALB/c 3T3 fibroblasts overexpressing the human receptor. Finally, IGF-I-promoted survival can be blocked with mAb specific for target epitopes, and their potential use in tumor cell growth control is discussed.

[Apical hypertrophic myocardiopathy and multiple fistulae between the coronary vessels and the left ventricle]. / Miocardiopatía hipertrófica apical y múltiples fístulas entre coronarias y ventrículo izquierdo.

A male patient presented with symptoms of angor under effort. Echocardiography and angiocardiography revealed apical hypertrophic myocardiopathy, associated with multiple fistulas connecting the anterior descending coronary artery and right coronary artery with the cavity of the left ventricle, as demonstrated by coronariography. We comment on the hypothesis that support a causal relationship between the two anomalies, microfistulas being the possible cause of the reactive hypertrophy through the induction of a coronary steal phenomenon with local ischemia; alternatively, the myocardiopathy itself might be the cause of microfistulas formation by inducing an anomaly in the Thebesius venous system. A pathogenic relationship is suggested between the syndrome of angor and these two rare pathological entities.

Design of peptides with improved affinities for anti-human chorionic gonadotropin monoclonal antibodies.

Three monoclonal antibodies, LF-hCG-6, -26 and -28, raised against holo-human chorionic gonadotropin and directed against its beta-subunit, have been used to design synthetic peptides with improved affinity. By PEPSCAN analyses with pinbound, overlapping nonapeptides, it was shown that the peptide consisting of amino acids (125-133) of the beta-subunit (i.e., PPSLPSPSR) reacted with monoclonal antibody (LF-hCG-6; the sequence (135-143) (i.e., PGPSDTPIL), with LF-hCG-28; and the C-terminal nonapeptide (137-145) (i.e., PSDTPILPQ), with LF-hCG-26. To determine amino acids essential for binding and those comprising the necessary amino acid core, and to establish the optimal length for binding reactivity, sets of replacement nonapeptides and overlapping octa- to dodecapeptides derived from the beta-subunit sequences (122-134) (i.e., KAPPPSLPSPSRL) and (132-145) (i.e., SRLPGPSDTPILPQ) were synthesized. Amino acid cores were as follows: beta-hCG (125-131) (i.e., PPSLPSP) for monoclonal antibody LF-hCG-6, beta-hCG (135-142) for LF-hCG-28 and beta-hCG (139-145) for LF-hCG-26. Based on the optimal length, parent peptide sequences [beta-hCG (125-133), (137-145) and (135-145)] were synthesized by conventional solid-phase procedures. In addition, based on the results with the replacement peptides, peptide derivatives were produced in which specific single improvements had been combined. The affinities of the monoclonal antibodies for the peptide derivatives, compared to the parent peptide sequences, were at least 700 times better for LF-hCG-6 reactive peptides (6.9 x 10(6) M-1 and < 10(4) M-1, respectively) and 130 times better for LF-hCG-26 reactive peptides (1.3 x 10(6) M-1 and < 10(4) M-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)