Dispositional mindfulness profiles in pregnant women: relationships with dyadic adjustment and symptoms of depression and anxiety

IntroductionPregnancy is a time of major transition that can be stressful for women. Dispositional mindfulness may protect individuals when they face stress. Recent studies have adopted a person-centered approach to examine the role of mindfulness by identifying subtypes of individuals based on their scores in five mindfulness facets. Latent profile analysis was used to identify different mindfulness profiles in a sample of pregnant women, and we explored the relationships between these profiles, depression and anxiety symptoms, and whether dyadic adjustment mediated these relationships.MethodA total of 535 women aged 18–45 years in their 26th week of pregnancy completed questionnaires regarding mindfulness, dyadic satisfaction and cohesion, and depression and anxiety symptoms.ResultsThree profiles were identified: (1) low mindfulness (53.8%), (2) moderate mindfulness (34.3%), and (3) non-judgmentally aware (11.9%). The most adaptive profile was the non-judgmentally aware profile. Compared to the low mindfulness profile, the non-judgmentally aware profile and the moderate mindfulness profile were related to fewer symptoms of depression and anxiety, and these relationships were partly mediated by dyadic satisfaction.DiscussionThese results suggest that analyzing each pregnant woman’s mindfulness profile can improve the prevention of and interventions for anxiety and depression

Tratamiento radioquirúrgico de los schwannomas del nervio vestibular. Evolución clínica y radiológica

Fue en 1951 cuando se inicia la radiocirugía, que consiste en aplicar una dosis de radiación alta y única en un volumen tumoral pequeño. En el año 2004, se empezaron a tratar pacientes en el CHUS con diferentes patologías mediante esta técnica. Hacemos un estudio retrospectivo descriptivo de una serie de 98 pacientes diagnosticados de schwannoma del nervio vestibular tratados mediante radiocirugía empleando un acelerador lineal (LINAC). Exponemos nuestra metodología, estudiamos el control volumétrico tumoral tras la validación estadística de la fórmula que nos aproxima a los volúmenes de seguimiento, y valoramos la afectación postradiocirugía en el V, VII y VIII pares craneales y otros efectos secundarios. En nuestra serie hemos obtenido un control del volumen tumoral superior al 90% no teniendo que operar a ningún paciente. En las curvas de evolución observamos una disminución progresiva del volumen y con afectación del V pc en un 4%, del VII pc en un 5% y del VIII pc en un 60%. Una paciente desarrolló un glioma radioinducido y falleció. A la vista de los resultados obtenido, consideramos que la radiocirugía es una técnica terapéutica de primera opción para el tratamiento de los SV al conseguirse un control del volumen tumoral muy alto con un bajo índice de complicaciones

Four Cholesterol-Recognition Motifs in the Pore-Forming and Translocation Domains of Adenylate Cyclase Toxin Are Essential for Invasion of Eukaryotic Cells and Lysis of Erythrocytes

Adenylate Cyclase Toxin (ACT or CyaA) is one of the important virulence factors secreted by Bordetella pertussis, the bacterium causative of whooping cough. ACT debilitates host defenses by production of unregulated levels of cAMP into the cell cytosol upon delivery of its N-terminal domain with adenylate cyclase activity (AC domain) and by forming pores in the plasma membrane of macrophages. Binding of soluble toxin monomers to the plasma membrane of target cells and conversion into membrane-integrated proteins are the first and last step for these toxin activities; however, the molecular determinants in the protein or the target membrane that govern this conversion to an active toxin form are fully unknown. It was previously reported that cytotoxic and cytolytic activities of ACT depend on membrane cholesterol. Here we show that ACT specifically interacts with membrane cholesterol, and find in two membrane-interacting ACT domains, four cholesterol-binding motifs that are essential for AC domain translocation and lytic activities. We hypothesize that direct ACT interaction with membrane cholesterol through those four cholesterol-binding motifs drives insertion and stabilizes the transmembrane topology of several helical elements that ultimately build the ACT structure for AC delivery and pore-formation, thereby explaining the cholesterol-dependence of the ACT activities. The requirement for lipid-mediated stabilization of transmembrane helices appears to be a unifying mechanism to modulate toxicity in pore-forming toxins.This research was funded by the Spanish Ministerio de Economía y Competitividad [grant number BFU2017–82758-P] and by the Basque Government [grant number IT1264-19]. J.A. was recipient of a fellowship from the University of Basque Country (UPV/EHU). RA holds a contract funded by the Fundación Biofisika Bizkaia

Characterization of the Intrinsic Phospholipase A1 Activity of Bordetella pertussis Adenylate Cyclase Toxin

Adenylate cyclase toxin (ACT, CyaA) is one of the important virulence factors secreted by the whooping cough bacterium Bordetella pertussis, and it is essential for the colonization of the human respiratory tract by this bacterium. Cytotoxicity by ACT results from the synergy between toxin's two main activities, production of supraphysiological cAMP levels by its N-terminal adenylate cyclase domain (AC domain), and cell membrane permeabilization, induced by its C-terminal pore-forming domain (hemolysin domain), which debilitate the host defenses. In a previous study we discovered that purified ACT is endowed with intrinsic phospholipase A1 (PLA) activity and that Ser in position 606 of the ACT polypeptide is a catalytic site for such hydrolytic activity, as part of G-X-S-X-G catalytic motif. Recently these findings and our conclusions have been directly questioned by other authors who claim that ACT-PLA activity does not exist. Here we provide new data on ACT phospholipase A1 characteristics. Based on our results we reaffirm our previous conclusions that ACT is endowed with PLA activity; that our purified ACT preparations are devoid of any impurity with phospholipase A activity; that ACT-S606A is a PLA-inactive mutant and thus, that Ser606 is a catalytic site for the toxin hydrolytic activity on phospholipids, and that ACT-PLA activity is involved in AC translocation.This study was supported by grants from the Basque Government (Grupos Consolidados IT849) and grant from the Spanish Ministerio de Economia y Competitividad (BFU2017-82758-P (AEI/FEDER, UE) to H.O

Membrane Repair Mechanisms against Permeabilization by Pore-Forming Toxins

Permeabilization of the plasma membrane represents an important threat for any cell, since it compromises its viability by disrupting cell homeostasis. Numerous pathogenic bacteria produce pore-forming toxins that break plasma membrane integrity and cause cell death by colloid-osmotic lysis. Eukaryotic cells, in turn, have developed different ways to cope with the effects of such membrane piercing. Here, we provide a short overview of the general mechanisms currently proposed for plasma membrane repair, focusing more specifically on the cellular responses to membrane permeabilization by pore-forming toxins and presenting new data on the effects and cellular responses to the permeabilization by an RTX (repeats in toxin) toxin, the adenylate cyclase toxin-hemolysin secreted by the whooping cough bacterium Bordetella pertussis, which we have studied in the laboratory.This study was supported by grants from the Basque Government (Grupos Consolidados IT849-13) and grant from the Spanish Ministerio de Economia y Competitividad (BFU2017-82758-PAEI/FEDER, UE)

Percepción del personal médico de atención primaria de salud acerca de sus funciones, formación y conocimientos en materia de salud laboral

ObjetivosEvaluar la percepción que el profesional médico de atención primaria de salud (PMAPS) tiene sobre sus funciones en prevención de riesgos laborales (PRL), así como sus conocimientos y habilidades en materia de salud laboral (SL).DiseñoEstudio descriptivo, transversal.EmplazamientoDepartamento de Salud 20 de la provincia de Alicante.ParticipantesTodos los PMAPS (n=104), con una participación del 80% (n=83).Mediciones principalesLos participantes autocumplimentaron un cuestionario específicamente desarrollado para el estudio. Se establecieron 16 cuestiones que abarcaban funciones en PRL y capacitación para desarrollarlas, así como cantidad y utilidad de formación recibidas en materia de SL.ResultadosEl PMAPS no percibe que tenga funciones en materia de PRL (mediana [Me], 2; rango intercuartílico [RI], 1-3). En mayor medida se consideró capacitado para identificar el origen laboral o no de una enfermedad atendida en su consulta (Me, 3; RI, 3-4). La formación en SL durante la licenciatura de medicina junto con la vía MIR se han identificado como las de menor cuantía (el 55,4 y el 60% de los entrevistados puntuaron en el valor 1 del cuestionario). EL PMAPS claramente ha considerado que una mayor formación en SL le ayudaría en su actividad diaria profesional; se obtuvieron puntuaciones de tipo alto (opciones de respuesta mayores o iguales a 4) en más del 70% de los entrevistados.ConclusionesEs necesario que se fomente la formación en SL para que el PMAPS se sienta parte integrante del personal sanitario con funciones en PRL y pueda adquirir los conocimientos y habilidades necesarios en materia de SL para su práctica médica habitual.ObjectivesTo evaluate the perception of primary health care medical staff (PHCMS) have on their functions in occupational risk prevention (ORP), as well as their knowledge and skills on the subject of occupational health (OH).DesignDescriptive cross-sectional study.SettingHealth Department 20 of Alicante province, Spain.ParticipantsAll PHCMS (N=104), with a participation of 80% (N=83).Primary MeasurementsThe participants self-completed a questionnaire specifically developed for the study. Sixteen questions were established and covered functions in ORP and skills for developing them, as well as the amount and usefulness of training received on the subject of OH.ResultsThe PHCMS did not perceive that they had functions as regards ORP (median [Me], 2; interquartile range [IR], 1-3). To a greater extent they considered themselves capable of identifying whether an illness seen in their clinic was of work origin or not (Me, 3; IR, 3-4).Training in OH as a medical student and in their medical internship (MIR) was identified as of minor importance (55.4% and 60%, respectively, of those surveyed scored a value of 1 in the questionnaire). The PHCMS obviously considered that better training in OH would help them in their daily professional activity. High scores were obtained for this (response options greater than or equal to 4) in more than 70% of the interviewees.ConclusionsTraining in OH must be encouraged so that PHCMS are seen to be health personnel with functions in ORP and are able to acquire the necessary knowledge and skills in OH for their routine medical practice

Understanding the Mechanism of Translocation of Adenylate Cyclase Toxin across Biological Membranes

Adenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18 integrin and delivers its N-terminal adenylate cyclase (AC) domain directly to the cell cytosol, where it catalyzes unregulated conversion of cytosolic ATP into cAMP upon activation by binding to cellular calmodulin. High cAMP levels disrupt bactericidal functions of the immune cells, ultimately leading to cell death. In spite of its relevance in the ACT biology, the mechanism by which its ≈400 amino acid-long AC domain is transported through the target plasma membrane, and is released into the target cytosol, remains enigmatic. This article is devoted to refresh our knowledge on the mechanism of AC translocation across biological membranes. Two models, the so-called “two-step model” and the recently-proposed “toroidal pore model”, will be considered.This study was supported by grants from the Basque Government (Grupos Consolidados IT849-13 and ETORTEK Program KK-2015/0000089). A.E. was recipient of a fellowship from the University of the Basque Country (UPV/EH) and D.G.-B. was recipient of a fellowship from the Bizkaia Biophysics Foundation

Cholesterol stimulates the lytic activity of Adenylate Cyclase Toxin on lipid membranes by promoting toxin oligomerization and formation of pores with a greater effective size

Several toxins acting on animal cells present different, but specific, interactions with cholesterol. Bordetella pertussis infects the human respiratory tract and causes whooping cough, a highly contagious and resurgent disease. Its virulence factor adenylate cyclase toxin (ACT) plays an important role in the course of infection. ACT is a pore-forming cytolysin belonging to the Repeats in ToXin (RTX) family of leukotoxins/hemolysins and is capable of permeabilizing several cell types and lipid vesicles. Previously, we observed that in the presence of cholesterol ACT induces greater liposome permeabilization. Similarly, recent reports also implicate cholesterol in the cytotoxicity of an increasing number of pore-forming RTX toxins. However, the mechanistic details by which this sterol promotes the lytic activity of ACT or of these other RTX toxins remain largely unexplored and poorly understood. Here, we have applied a combination of biophysical techniques to dissect the role of cholesterol in pore formation by ACT. Our results indicate that cholesterol enhances the lytic potency of ACT by promoting toxin oligomerization, a step which is indispensable for ACT to accomplish membrane permeabilization and cell lysis. Since our experimental design eliminates the possibility that this cholesterol effect derives from toxin accumulation due to lateral lipid phase segregation, we hypothesize that cholesterol facilitates lytic pore formation, by favoring a toxin conformation more prone to protein-protein interactions and oligomerization. Our data shed light on the complex relationship between lipid membranes and protein toxins acting on these membranes. Coupling cholesterol binding, increased oligomerization and increased lytic activity is likely pertinent for other RTX cytolysins.Rocío Alonso is gratefully acknowledged for excellent technical assistance. This study was supported by grants from the Spanish Ministerio de Economia y Competitividad BFU2017-82758-P (H.O.) and of Basque Government (Grupos Consolidados IT1264-19). D.G.B was recipients of a fellowship from the Bizkaia Biophysics Foundation, and JA was recipient of a fellowship from the Basque Government