Sources analysis and equivalent toxicity assessment of PAHs impacted sediments in Bahia Blanca Estuary, Argentina

Se presenta un estudio exhaustivo de sedimentos del estuario de Bahía Blanca (Argentina) para determinar su impacto por Hidrocarburos Aromáticos Policíclicos (PAHs). Los sedimentos fueron procesados siguiendo protocolos de la Environmental Protection Agency (EPA, USA) y analizados por Cromatografía Gaseosa-Espectrometría de Masas, hallándose un rango de concentraciones total, desde 103 a más de 2,000 ng.g -1 p.s. (p.s.= peso seco; Total PAHs = sumatoria de 17 PAHs), una concentración media de 527 ± 114 ng.g -1 y una mediana de 507 ng.g -1 . Se demostró la existencia de un nivel dinámico de contaminación por PAHs, definido por valores bajos a moderados que incluyeron zonas puntuales con altos niveles. El análisis de origen mediante el uso de índices moleculares determinó un predominio de deposiciones pirolíticas sobre las de origen petrogénico, siendo dominantes las emisiones provenientes de la quema de biomasa durante los meses más cálidos. La calidad ecotoxicológica de los sedimentos se abordó utilizando el enfoque de niveles guía, hallándose para la mayoría de los sitios muestreados una predicción de efectos adversos infrecuentes sobre la biota adyacente, con sitios puntuales para los cuales se predijo la aparición frecuente de efectos. Utilizando el concepto de equivalentes de Benzo-a-pireno se calculó su carga total, la cual se halló en ocasiones por sobre los valores indicados en diversas regulaciones internacionales. Finalmente se evaluó la dosis carcinogénica aportada por los 7 PAHs carcinogénicos y su perfil de concentraciones se contrastó estadísticamente con otros sitios costeros del mundo utilizando análisis de grupos jerarquizados.This paper presents a comprehensive survey of PAHs in coastal sediments of Bahia Blanca, Argentina and provides useful information of their levels of concentration, sources, ecotoxicological assessment and carcinogenic PAHs profile of local emissions. Sediments were analyzed following Environmental Protection Agency (EPA, USA) protocols by means of Gas Chromatography-Mass Spectrometry, showing total concentrations of PAHs in a range from 103 to more than 2,000 ng.g -1 (mean: 527 ± 114 ng.g -1 ; median: 507 ng.g -1 ). A dynamic state of PAHs pollution was demonstrated for the area which was defined by widespread low to moderate levels, but including punctual zones with high pollution processes. Molecular ratios calculations determined a generalized overimposition of pyrolitic PAHs over the petrogenic input. The pyrolitic pattern moved to a biomass burning origin during summer, the period of highest recorded fires. In addition, the ecotoxicological guidelines approach for PAHs chemical concentrations in sediment defined a rare occurrence of biological effects for the majority of sampled sites; however, frequent effects were expected for punctual locations. Further, Total Benzo-a-pyrene equivalents from several sampling stations were found to be above international regulations. Finally, the PAHs carcinogenic dose was calculated using the BaP equivalent factors approach and compared with other worldwide coastal studies by means of Hierarchical Cluster Analysis.Fil: Arias, Andres Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur; ArgentinaFil: Marcovecchio, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Tecnológica Nacional; Argentina. Universidad FASTA "Santo Tomas de Aquino"; ArgentinaFil: Freije, Rubén Hugo. Universidad Nacional del Sur; ArgentinaFil: Ponce Velez, Guadalupe. Universidad Nacional Autónoma de México. Instituto de Ciencias del Mar y Limnología; MéxicoFil: Vazquez Botello, Alfonso. Universidad Nacional Autónoma de México. Instituto de Ciencias del Mar y Limnología; Méxic

Effects of a High-Intensity Interval Training Program Versus a Moderate-Intensity Continuous Training Program on Maximal Oxygen Uptake and Blood Pressure in Healthy Adults: Study Protocol for a Randomized Controlled Trial

Background: Participation in aerobic exercise generates increased cardiorespiratory fitness, which results in a protective factor for cardiovascular disease and all-cause mortality. High-intensity interval training might cause higher increases in cardiorespiratory fitness in comparison with moderate-intensity continuous training; nevertheless, current evidence is not conclusive. To our knowledge, this is the first study to test the effect of high-intensity interval training with total load duration of 7.5 min per session. Methods: A randomized controlled trial will be performed on two groups of healthy, sedentary male volunteers (n = 44). The study protocol will include 24 exercise sessions, three times a week, including aerobic training on a treadmill and strength training exercises. The intervention group will perform 15 bouts of 30 s, each at an intensity between 90 % and 95 % of maximal heart rate. The control group will complete 40 min of continuous exercise, ranging between 65 % and 75 % of maximal heart rate. The primary outcome measure to be evaluated will be maximal oxygen uptake (VO2max), and systolic and diastolic blood pressure will be evaluated as secondary outcome measures. Waist circumference, body mass index, and body composition will also be evaluated. Discussion: Epidemiological evidence shows the link between VO2max and its association with chronic conditions that trigger CV

Interaction of Bupropion with Muscle-Type Nicotinic Acetylcholine Receptors in Different Conformational States

To characterize the binding sites and the mechanisms of inhibition of bupropion on muscle-type nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The results established that bupropion: (a) inhibits epibatidine-induced Ca2+ influx in embryonic muscle AChRs, (b) inhibits adult muscle AChR macroscopic currents in the resting/activatable state with ~100-fold higher potency compared to that in the open state, (c) increases desensitization rate of adult muscle AChRs from the open state and impairs channel opening from the resting state, (d) inhibits [3H]TCP and [3H]imipramine binding to the desensitized/carbamylcholine-bound Torpedo AChR with higher affinity compared to the resting/α-bungarotoxin-bound AChR, (e) binds to the Torpedo AChR in either state mainly by an entropy–driven process, and (f) interacts with a binding domain located between the serine (position 6’) and valine (position 13’) rings, by a network of van der Waals, hydrogen bond, and polar interactions. Collectively our data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening. The remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Bupropion interacts with a luminal binding domain shared with PCP that is located between the serine and valine rings, and this interaction is mediated mainly by an entropy-driven process.Fil: Arias, Hugo Rubén. Midwestern University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gumilar, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Rosenberg, Avraham. National Institutes of Health; Estados UnidosFil: Targowska Duda, Katarzyna M.. Medical University of Lublin; PoloniaFil: Feuerbach, Dominik. Novartis Institutes for Biomedical Research; SuizaFil: Jozwiak, Krzysztof. Medical University of Lublin; PoloniaFil: Moaddel, Ruin. National Institutes of Health; Estados UnidosFil: Wainer, Irving W.. National Institutes of Health; Estados UnidosFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentin

Herbert C. Kelman and Peace Psychology

En este artículo se revisa la vida y obra de Herbert Kelman (1927-2022), uno de los psicólogos sociales más influyentes del siglo XX y del presente siglo. Sus teorías han tenido un impacto favorable en la resolución de conflictos internacionales, a partir de la base de evidencia experimental y de su intervención en diversos eventos internacionales en el medio oriente y otras partes del mundo. Además, fue uno de los principales promotores de la psicología de la paz y publicó una amplia diversidad de artículos, capítulos de libro y libros con una favorable recepción en el campo de la psicología social. También fue presidente de la Sociedad Interamericana de Psicología (SIP) entre 1976 y 1979, con un despliegue de funciones que son objeto de nuestro análisis. Por todo ello, Kelman es un autor, cuya obra merece ser revisada y analizada con motivo de su reciente fallecimiento, para dar continuidad a sus ideas y sus aportes en el campo de la resolución de conflictos.This article reviews the life and work of Herbert Kelman (1927-2022), one of the most influential social psychologists of the 20th century and of the present century. His theories have had a favorable impact on the resolution of international conflicts, based on experimental evidence and his intervention in various international events in the Middle East and other parts of the world. In addition, he was one of the leading promoters of the psychology of peace and published a wide variety of a well-received articles, book chapters, and books in the field of social psychology. He also was president of the Interamerican Society of Psychology (ISP) between 1976 and 1979, with a display of functions that are the object of our analysis. For all these reasons, Kelman is an author, whose work deserves to be reviewed and analyzed on the occasion of his recent death, to give continuity to his ideas and his contributions in the field of conflict resolution.Fil: Arias Gallegos, Walter L.. Universidad Catolica de San Pablo; PerúFil: Klappenbach, Hugo Alberto Arturo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Psicologia. Instituto de Ciencias Computacionales, Cognitivas, Psicológicas y Sociales.; ArgentinaFil: Ardila, Rubén. Universidad Nacional de Colombia; ColombiaFil: López López, Wilson. Pontificia Universidad Javeriana; ColombiaFil: Caycho Rodríguez, Tomás. Universidad Cientifica del Sur

Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors

Identification of all residues involved in the recognition and binding of cholinergic ligands (e.g. agonists, competitive antagonists, and noncompetitive agonists) is a primary objective to understand which structural components are related to the physiological function of the nicotinic acetylcholine receptor (AChR). The picture for the localization of the agonist/competitive antagonist binding sites is now clearer in the light of newer and better experimental evidence. These sites are located mainly on both α subunits in a pocket approximately 30-35 A above the surface membrane. Since both α subunits are identical, the observed high and low affinity for different ligands on the receptor is conditioned by the interaction of the α subunit with other non-α subunits. This molecular interaction takes place at the interface formed by the different subunits. For example, the high-affinity acetylcholine (ACh) binding site of the muscle-type AChR is located on the αδ subunit interface, whereas the low-affinity ACh binding site is located on the αγ subunit interface. Regarding homomeric AChRs (e.g. α7, α8, and α9), up to five binding sites may be located on the αα subunit interfaces. From the point of view of subunit arrangement, the γ subunit is in between both α subunits and the δ subunit follows the α aligned in a clockwise manner from the γ. Although some competitive antagonists such as lophotoxin and α-bungarotoxin bind to the same high- and low-affinity sites as ACh, other cholinergic drugs may bind with opposite specificity. For instance, the location of the high- and the low-affinity binding site for curare-related drugs as well as for agonists such as the alkaloid nicotine and the potent analgesic epibatidine (only when the AChR is in the desensitized state) is determined by the αγ and the αδ subunit interface, respectively. The case of α-conotoxins (α-CoTxs) is unique since each α-CoTx from different species is recognized by a specific AChR type. In addition, the specificity of α-CoTxs for each subunit interface is species-dependent.In general terms we may state that both α subunits carry the principal component for the agonist/competitive antagonist binding sites, whereas the non-α subunits bear the complementary component. Concerning homomeric AChRs, both the principal and the complementary component exist on the α subunit. The principal component on the muscle-type AChR involves three loops-forming binding domains (loops A-C). Loop A (from mouse sequence) is mainly formed by residue Y93, loop B is molded by amino acids W149, Y152, and probably G153, while loop C is shaped by residues Y190, C192, C193, and Y198. The complementary component corresponding to each non-α subunit probably contributes with at least four loops. More specifically, the loops at the γ subunit are: loop D which is formed by residue K34, loop E that is designed by W55 and E57, loop F which is built by a stretch of amino acids comprising L109, S111, C115, I116, and Y117, and finally loop G that is shaped by F172 and by the negatively-charged amino acids D174 and E183. The complementary component on the δ subunit, which corresponds to the high-affinity ACh binding site, is formed by homologous loops. Regarding α-neurotoxins, several snake and α-CoTxs bear specific residues that are energetically coupled with their corresponding pairs on the AChR binding site. The principal component for snake α-neurotoxins is located on the residue sequence α1W184-D200, which includes loop C. In addition, amino acid sequence 55-74 from the α1 subunit (which includes loop E), and residues γL119 (close to loop F) and γE176 (close to loop G) at the low-affinity binding site, or δL121 (close to the homologous region of loop G) at the high-affinity binding site, are involved in snake α-neurotoxin binding. The above expounded evidence indicates that each cholinergic molecule binds to specific residues which form overlapping binding sites on the AChR.Monoclonal antibodies have been of fundamental importance in the elucidation of several aspects of the biology of the AChR. Interestingly, certain antibodies partially overlap with the agonist/competitive antagonist binding sites at multiple points of contact. In this regard, a monoclonal antibody directed against the high-affinity ACh binding site (αδ subunit interface) induced a structural change on the AChR where the low-affinity ACh locus (αγ subunit interface) approached to the lipid membrane.The α subunits also carry the binding site for noncompetitive agonists. Noncompetitive agonists such as the acetylcholinesterase inhibitor (-)-physostigmine, the alkaloid galanthamine, and the opioid derivative codeine are molecules that weakly activate the receptor without interacting with the classical agonist binding sites. This binding site was found to be located at K125 in an amphipathic domain of the extracellular portion of the α1 subunit. Interestingly, the neurotransmitter 5-hydroxytryptamine (5-HT) also binds to this site and enhances the agonist-induced ion flux activity. This suggests that 5-HT may act as an endogenous modulator (probably as co-agonist) of neuronal-type AChRs. The enhancement of the agonist-evoked currents elicited by noncompetitive agonists seems to be physiologically more important than their weak agonist properties.Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentin

Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors

The nicotinic acetylcholine receptor (AChR) is the archetype of the Cys-loop ligand-gated ion channel'receptor superfamily. Noncompetitive antagonists inhibit the AChR without interacting directly with agonist sites. Among non-competitive antagonists, general and local anesthetics have been used for decades to study the structure and function of muscle- as well as neurorial-type AChRs. In this review, we address and update all information regarding the characterization of binding sites and the mechanism of action for n-alkanols, barbiturates, inhalational and dissociative general anesthetics, as well as for tertiary and quaternary local anesthetics. The experimental evidence outlined in this review suggest that: (1) several neuronal-type AChRs might be targets for the pharmacological action of distinct anesthetics; (2) the molecular components of a specific anesthetic locus on a certain receptor type are different from the structural determinants of the site for the same anesthetic on a different receptor type; (3) there are unique binding sites for distinct anesthetics in the same receptor; (4) the affinity of a specific anesthetic depends on the AChR conformational state; (5) anesthetics may inhibit AChRs by different mechanisms including open-channel-blocking, augmenting the desensitization process, and/or inactivating the opening of resting receptors; and (6) some anesthetics may potentiate AChR activity.Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentina. Western University of Health Sciences; Estados UnidosFil: Bhumireddy, Pankaj. Western University of Health Sciences; Estados Unido

La cultura de la seguridad del paciente: enfoques y metodologías para su medición

Introducción: el concepto de cultura de la seguridad del paciente se desarrollae n las denominadas “organizaciones de alta confiabilidad”, como estrategia para enfrentar la problemática de los eventos adversos.Objetivo:revisar los enfoques que han predominado en cultura de la seguridad del paciente y describir algunas herramientas que se han utilizado para su medición.Metodología: revisión narrativa enfocada en la conceptualización de cultura de la seguridad.Resultados: el término cultura de la seguridad es utilizado por la literatura con varios significados. La polisemia del término y en particular la confusión con la noción de “clima de seguridad”, implica también confusiones en los métodos e interpretación de las mediciones.Se identifican dos enfoques conceptuales básicos en el estudio de la cultura de la seguridad: el antropológico y el funcionalista, siendo este último el predominante en el desarrollo de instrumentos utilizados para su medición; estos últimos, sin embargo, presentan constructos y propiedade smétricas variables.Conclusión: el estudio de la seguridad del paciente, como categoría en desarrollo, debería utilizar los enfoques de medición disponibles con una mirada crítica, integrando técnicas de entrevista y estudios cualitativos, en especial de tipo etnográfico, que suministren información más integral y útil en la toma de decisiones encaminadas a mejorar la seguridad y confiabilidad de la atención médica. AbstractIntroduction: The notion of Patient Safety Culture has been developed strongly linked to the concept of “High Reliability Organizations”, as a strategy to face the problem of adverse events.Objective: To review the approaches that have prevailed in Patient Safety Culture and describe some tools that havebeen used for its measurement.Methodology: Narrative review focused onthe conceptualization of safety culture.Results: Technical literature uses the term safety culture with several meanings. The multiple meanings of the term, and particularly the vagueness with the term “safety climate” also involve confusions in the methods and interpretations of measurements. Two main conceptual approaches to the study of the safety culture were identified: the anthropological and the functionalist approaches, the latter being predominant in the development of instruments used to measure Patient Safety Culture, however, their constructs and their metric properties are widely heterogeneous.Conclusion: The study of patient safety as developing category, one should use the available measurement approaches with a critical view, integrating information from other sources such as interviews and qualitative studies, including ethnographic approach, to provide more comprehensive and useful tools in the decision-making process aimed at improving the safety and reliability of medical care

Activation and modulation of the nicotinic receptor

Nicotinic acetylcholine receptors (AChRs) are the best characterized ion channels representing the Cys-loop receptor superfamily. AChRs have all the machinery to recognize the neurotransmitter ACh and other agonists such as nicotine, and to transduce the agonist-induced conformational changes into the opening of the intrinsic cation channel. The gating machinery couples ligand binding, located at the extracellular portion, to the opening of the ion channel, located at the transmembrane region. The interface between the extracellular and the transmembrane domains is considered one of the most important structural and functional features for the process of gating. And finally, in the prolonged presence of agonists, the AChR becomes desensitized. Several drugs affect the functioning of these receptors. Among them, positive allosteric modulators (PAM) have acquired importance since are novel drugs for several neurological diseases. PAMs do not bind to the orthostetic binding sites but allosterically enhance the activity elicited by agonists by increasing the gating process and/or by decreasing desensitization. Instead, negative allosteric modulators (NAMs) produce the opposite effects. Interestingly, this negative effect is similar to that found for another class of allosteric drugs, i.e. non competitive antagonists (NCAs). However, the main difference between both categories of drugs is based on their distinct binding site locations. Although both NAMs and NCAs do not bind to the agonist sites, NACs bind to sites located in the ion channel, whereas NAMs bind to nonluminal sites. Interestingly, PAMs and NAMs might be developed as potential medications for the treatment of several diseases involving AChRs including, dementia-, skin-, and immunological-related diseases, drug addiction, and cancer. More exciting is the potential combination of specific agonists with PAMs. However, we are still in the beginning of understanding how these compounds act and how these drugs can be used therapeutically.Fil: Arias, Hugo Rubén. Midwestern University; Estados UnidosFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentin

α-Conotoxins

α-Conotoxins (α-CgTxs) are a family of Cys-enriched peptides found in several marine snails from the genus Conus. These small peptides behave pharmacologically as competitive antagonists of the nicotinic acetylcholine receptor (AChR). The data indicate that (1) α-CgTxs are able to discriminate between muscle- and neuronal-type AChRs and even among distinct AChR subtypes; (2) the binding sites for α-CgTxs are located, like other cholinergic ligands, at the interface of α and non-α subunits (γ, δ, and ε for the muscle-type AChR, and β for several neuronal-type AChRs); (3) some α-CgTxs differentiate the high- from the low-affinity binding site found on either α/non-α subunit interface; and that (4) specific residues in the cholinergic binding site are energetically coupled with their corresponding pairs in the toxin stabilizing the α-CgTx-AChR complex. The α-CgTxs have proven to be excellent probes for studying the structure and function of the AChR family.Fil: Arias, Hugo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentina. Texas Teach University Health Sciences Center; Estados UnidosFil: Blanton, Michael P. Texas Teach University Health Sciences Center; Estados Unido