Theoretical insight into the rearrangement of sulfur atoms on the Ni- and Cu-doped MoS2 S-edge induced by hydrogen adsorption under HDS reaction conditions.

Density functional theory (DFT) calculations and an atomistic thermodynamic approach were used to study the geometric rearrangement of sulfur atoms on the Ni- and Cu-doped MoS2 S-edge upon hydrogen adsorption. Under HDS conditions, thermodynamically stable hydrogenated structures were identified as SH groups on the undoped S-edge with 100% sulfur coverage, on the Ni-doped S-edge with 50% sulfur coverage and on the Cu-doped S-edge with 25% sulfur coverage. It was found that the rearrangement of the S atoms is essential to reach the most stable state at the edge for the undoped and Ni-doped S-edge. Hydrogen adsorption on the Ni-doped S-edge leads to the greatest amount of S rearrangement (ΔERearrang = 0.93 eV/H2). Our results suggest that under the reaction conditions, the H2 dissociative adsorption process is strongly coupled to the rearrangement of the sulfur atoms. By examining the differential hydrogen adsorption energy on the most stable edge structures, we found a plausible explanation for the trend in the hydrogenation activity of the doped edges. Our results suggest that Ni enhances the hydrogenation activity of the S-edge by decreasing the S-H bond strength, while Cu poisons it by increasing the S-H bond strength.

Application of the unified protocol for transdiagnostic treatment of emotional disorders in post-bariatric surgery patients: an effectiveness and feasibility study in group format

La obesidad es un grave problema de salud con implicaciones globales. La cirugía bariátrica (CB) es el tratamiento más utilizado y eficaz, pero hay pacientes que no pierden una cantidad sustancial de peso, hecho que se ha relacionado con la presencia de síntomas de alimentación emocional, ansiedad y depresión. El objetivo de este estudio es analizar la viabilidad y efectividad de una intervención basada en la regulación de las emociones denominada Protocolo Unificado (PU), aplicada en formato grupal a 6 pacientes post-CB que presentan trastornos/síntomas emocionales. Los resultados tras el tratamiento mostraron altas tasas de asistencia y satisfacción con el PU, y mejorías estadísticamente significativas para el neuroticismo, los síntomas de los trastornos alimentarios y la alimentación emocional. En el seguimiento a los 6 meses, se muestran reducciones significativas en los síntomas de ansiedad, neuroticismo, inadaptación y disregulación (d = 0.83-1.46) y el índice de masa corporal se mantuvo estable a lo largo del tiempo. Estos resultados preliminares son esperanzadores sobre la viabilidad y efectividad del PU para tratar la disregulación emocional en pacientes después de la CB.(AU)

Obesity is a serious health problem with global implications. Bariatric surgery (BS) is the most used and effective treatment, but there are patients who do not lose a substantial amount of weight, a fact that has been related with the presence of emotional eating, anxiety and depression symptoms. The aim of this study is to analyze the effectiveness and feasibility of an emotion regulation-based intervention called Unified Protocol (UP), applied in group format to 6 post-BS patients presenting emotional disorders/symptoms. Results at post-treatment shown high attendance rates and satisfaction with the UP scores and significant improvements on neuroticism, eating disorders symptoms and emotional eating. At 6-month follow-up we found significant reductions on anxiety symptoms, neuroticism, maladjustment and dysregulation (d = 0.83-1.46) and the body mass index remained stable over time. These preliminary results are encouraging about the effectiveness and feasibility of the UP to treat emotional dysregulation in patients after BS.(AU)

Design, assembly and validation of a low-cost, high-fidelity simulator for heart exploration.

INTRODUCTION: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. OBJECTIVE: To develop and validate a low-cost, high-fidelity simulator for heart exploration. METHODS: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. RESULTS: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. CONCLUSIONS: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

INTRODUCCIÓN: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. OBJETIVO: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. MÉTODOS: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. RESULTADOS: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. CONCLUSIONES: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

Diseño, elaboración y validación de un simulador realista y de bajo costo para exploración cardiaca / Design, assembly and validation of a low-cost, high-fidelity simulator for heart exploration

Resumen Introducción: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. Objetivo: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. Métodos: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. Resultados: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. Conclusiones: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

Abstract Introduction: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. Objective: To develop and validate a low-cost, high-fidelity simulator for heart exploration. Methods: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. Results: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. Conclusions: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

Rehabilitación cardíaca: escenario de simulación en alumnos de pregrado de medicina y fisioterapia / Cardiac rehabilitation: a simulated case in undergraduate medicine and physical therapy students

INTRODUCCIÓN: La educación interprofesional favorece que profesionales de diversas disciplinas trabajen en conjunto para mejorar el abordaje terapéutico del paciente. OBJETIVO: Valorar el desempeño de los alumnos de fisioterapia y medicina sobre el trabajo interprofesional durante un escenario de simulación para el manejo de la rehabilitación cardíaca con paciente estandarizado. Sujetos y métodos: Participaron un total de 331 alumnos de medicina y fisioterapia. Se diseñó un escenario de simulación sobre rehabilitación cardíaca, una lista de comprobación de habilidades y una encuesta de opinión. Se formaron equipos compuestos por alumnos de ambas licenciaturas y se calcularon los porcentajes de ambos instrumentos. RESULTADOS: Para los alumnos de medicina, el ítem que obtuvo mayor respuesta fue el 1 (82,3%), mientras que el que tuvo menor respuesta fue el ítem 6 (27,8%). Para los alumnos de fisioterapia, el ítem 7 tuvo el mayor porcentaje (100%), mientras que el que tuvo menor porcentaje fue el ítem 6 (16,7%). Las opiniones favorables se obtuvieron en un 90% de calificación entre el totalmente de acuerdo y de acuerdo. CONCLUSIÓN: Se requiere diseñar escenarios e instrumentos que permitan valorar el trabajo interprofesional y documentar los resultados, así como el desarrollo de estudios longitudinales que muestren la efectividad de la educación interprofesional en profesionales de salud

INTRODUCTION: Interprofessional education encourages professionals from various disciplines to work together to improve the patient's therapeutic approach. AIM: To assess the performance of physiotherapy and medicine students on interprofessional work during a simulation scenario for the management of cardiac rehabilitation with a standardized patient. Subjects and methods: A total of 331 medical and physical therapy students participated. A simulation scenario on cardiac rehabilitation, a skills checklist, and opinion survey were designed. Teams made up of students from both degrees were formed and percentages of both instruments were calculated. RESULTS: For medical students, the item with the highest response was 1 (82.3%), while the item with the lowest response was item 6 (27.8%). For physiotherapy students, item 7 had the highest percentage (100%), while the one with the lowest percentage was item 6 (16.7%). The favorable opinions were obtained in a 90% rating between the totally agree and agree. CONCLUSION: It is required to design scenarios and instruments that allow evaluating interprofessional work and documenting the results, as well as the development of longitudinal studies that show the effectiveness of interprofessional education in health professionals

[Clinical and pathophysiological description of nummular headaches: a case series]. / Descripción clínica y fisiopatológica de la cefalea numular: serie de casos.

INTRODUCTION: Nummular headache was initially described as an infrequent primary headache characterised by chronic circumscribed mild-to-moderate pain in a small area of the head that may present with exacerbations. Since its initial description, dozens of cases of nummular headache have been reported which broaden the clinical and pathophysiological spectrum. AIMS: To review and establish the clinical characteristics of nummular headache, to analyse the epidemiology in our setting and to clarify some unanswered pathophysiological issues. PATIENTS AND METHODS: The study involved 83 cases (42 women and 41 men) who were diagnosed with nummular headache from July 2008 and followed up until 2018 at the Fundacion Alcorcon Hospital. The mean age of onset was 46 years. The time to diagnosis was seven months. RESULTS: The pain was moderate-intense and oppressive, with exacerbations in 62.5% of cases. The average size of the symptomatic area was 2.4 ± 0.7 cm, with a parietal (47%), temporal (24%), frontal (12%) or occipital (6%) location. It presented a chronic (82%) or episodic (18%) pattern. Symptoms of local sensory dysfunction were observed in 25 patients and three others showed skin alterations. Spontaneous remission was observed in 36% of cases, and the most commonly used drugs were non-steroidal anti-inflammatory drugs, paracetamol and gabapentin. Botulinum toxin was effective. CONCLUSIONS: Nummular headache is a disorder with well-defined characteristics and is considered an entity in its own right. Our data indicate that its origin lies in the epicranial structures. The conjunction of pain, sensory dysfunction and trophic disorders suggests a local form of a complex regional syndrome.

TITLE: Descripción clínica y fisiopatológica de la cefalea numular: serie de casos.Introducción. La cefalea numular se describió inicialmente como una cefalea primaria infrecuente caracterizada por dolor circunscrito crónico en una pequeña área craneal, de intensidad leve-moderada y que puede presentar exacerbaciones. Desde su descripción inicial se han publicado decenas de casos de cefalea numular que amplían el espectro clínico y fisiopatológico. Objetivos. Revisar y establecer las características clínicas de la cefalea numular, analizar la epidemiología en nuestro medio y aclarar incógnitas fisiopatológicas. Pacientes y métodos. Se estudiaron 83 casos (42 mujeres y 41 varones), que fueron diagnosticados de cefalea numular desde julio de 2003 a julio de 2008, y seguidos hasta 2018 en el Hospital Universitario Fundación Alcorcón. La edad media de inicio fue de 46 años. El tiempo de evolución hasta el diagnóstico fue de siete meses. Resultados. El dolor fue moderado-intenso y opresivo, con exacerbaciones en el 62,5% de los casos. El tamaño medio del área sintomática fue de 2,4 ± 0,7 cm, con una localización parietal (47%), temporal (24%), frontal (12%) u occipital (6%). Presentó un patrón crónico (82%) o episódico (18%). Mostraron síntomas de disfunción sensitiva local 25 pacientes, y otros tres, cambios en la piel. La remisión espontánea se observó en el 36% de los casos, y los fármacos más utilizados fueron los antiinflamatorios no esteroideos, el paracetamol y la gabapentina. La toxina botulínica fue eficaz. Conclusiones. La cefalea numular es un trastorno con características bien definidas y con entidad propia. Nuestros datos indican que su origen está en las estructuras epicraneales. La conjunción de dolor, disfunción sensitiva y alteraciones tróficas indica una forma local de síndrome regional complejo.

Multimorbidade em idosos de um município do nordeste brasileiro: prevalência e fatores associados / Multimorbity in elderly municipal of northeast Brazil: prevalence and associated factors / en ancianos de un municipio del nordeste brasileño: prevalencia y factores asociados

RESUMO Objetivo Estimar a prevalência e os fatores associados à presença de multimorbidade na população idosa do município de Ibicuí - BA. Métodos Estudo realizado com 310 idosos com idade > 60 anos, de ambos os sexos, residentes no município de Ibicuí - BA. Foram coletadas informações sociodemográ-ficas e informações pessoais, condições de vida, hábitos de vida, massa corporal, estatura e presença de multimorbidade. Utilizou-se análise descritiva e foram estimadas razões de prevalência de multimorbidade, segundo variáveis de interesse. Como medida de significância estatística foi utilizado o teste de Qui-quadrado de Pearson, adotando-se p≤0,05. A análise multivariada hierarquizada por Regressão de Poisson foi empregada após análise bivariada para seleção das variáveis independentes (p<0,20). Resultados A prevalência geral de multimorbidade foi de 80,3%. Na análise multivariada hierarquizada, apresentaram associação significativa, as variáveis sexo e renda mensal (p<0,05). Os resultados mostraram uma elevada prevalência de multimorbidade na população investigada e essa condição foi mais acentuada entre as mulheres e aqueles com menor nível económico. Conclusões Faz-se necessário redirecionar o planejamento das ações de saúde no município, com mudanças na política de atenção à saúde do idoso e, principalmente, nas redes de suporte social que amparam esses indivíduos, uma vez que, nesta localidade, a presença de multimorbidade esteve relacionada a questões socioeconómicas.(AU)

ABSTRACT Objective To estimate the prevalence and the factors associated with the presence of multimorbidity in the elderly population of the municipality of Ibicuí - BA. Methods This study was carried out with 310 elderly individuals, aged > 60 years old, of both sexes, living in the municipality of Ibicuí - BA. Sociodemographic information and personal information, living conditions, life habits, body mass, stature and presence of multimorbidity were collected. The descriptive analysis was used and multimorbidity prevalence ratios were estimated according to variables of interest. As a measure of statistical significance, the qui-quadrado de Pearson test was used, adopting p≤0.05. The multivariate analysis hierarchized by Poisson regression was employed after bivariate analysis to select the independent variables (p<0.20). Results The general prevalence of multimorbidity was 80.3%. The hierarchical multi-varied analysis showed the variables of gender and monthly income (p<1.5) were significantly related to the problem. The results reveal also a high prevalence of multimorbidity in the studied population. Mainly women and the poorest suffer from it. Conclusions It is necessary to redirect the planning of health actions in the municipality, with changes in the health care policy of the elderly, and especially in the social support networks that support these individuals, considering that in this locality the presence of multimorbidity was related to socio-economic grounds.(AU)

RESUMEN Objetivo Estimar la prevalencia y los factores asociados a la presencia de multimorbilidad en la población anciana del municipio de Ibicuí - BA. Métodos Estudio realizado con 310 ancianos con edad > 60 años, de ambos sexos, residentes en el municipio de Ibicuí-BA. Se recigió información sociodemográfica y personales, condiciones de vida, hábitos de vida, masa corporal, estatura y presencia de multimorbilidad. Se utilizó análisis descriptivo y se estimaron razones de prevalencia de multimorbilidad, según variables de interés. Como medida de significancia estadística se utilizó la prueba de Qui-cuadrado de Pearson, adoptando p≤0,05. El análisis multivariado jerarquizado por Regresión de Poisson fue empleada después del análisis bivariado para la selección de las variables independientes (p<0,20). Resultados La prevalencia general de multimorbilidad fue del 80,3%. En el análisis multivariado jerarquizado, presentaron asociación significativa las variables de sexo y renta mensual (p <0,05). Los resultados mostraron una elevada prevalencia de multimorbilidad en la población investigada y esa condición fue más acentuada entre las mujeres y aquellos con menor nivel económico. Conclusiones En ese sentido, se hace necesario reorientar la planificación de las acciones de salud en el municipio, con cambios en la política de atención a la salud del anciano y, principalmente, en las redes de soporte social que amparan a esos individuos, ya que, en esta localidad, la presencia de multimorbilidades estuvo relacionada con cuestiones socioeconómicas.(AU)

[Multimorbity in elderly municipal of northeast Brazil: prevalence and associated factors]. / Multimorbidade em idosos de um município do nordeste brasileiro: prevalência e fatores associados.

OBJECTIVE: To estimate the prevalence and the factors associated with the presence of multimorbidity in the elderly population of the municipality of Ibicuí - BA. METHODS: This study was carried out with 310 elderly individuals, aged > 60 years old, of both sexes, living in the municipality of Ibicuí - BA. Sociodemographic information and personal information, living conditions, life habits, body mass, stature and presence of multimorbidity were collected. The descriptive analysis was used and multimorbidity prevalence ratios were estimated according to variables of interest. As a measure of statistical significance, the qui-quadrado de Pearson test was used, adopting p≤0.05. The multivariate analysis hierarchized by Poisson regression was employed after bivariate analysis to select the independent variables (p<0.20). RESULTS: The general prevalence of multimorbidity was 80.3%. The hierarchical multi-varied analysis showed the variables of gender and monthly income (p<1.5) were significantly related to the problem. The results reveal also a high prevalence of multimorbidity in the studied population. Mainly women and the poorest suffer from it. CONCLUSIONS: It is necessary to redirect the planning of health actions in the municipality, with changes in the health care policy of the elderly, and especially in the social support networks that support these individuals, considering that in this locality the presence of multimorbidity was related to socio-economic grounds.

The bending machine: CO2 activation and hydrogenation on δ-MoC(001) and ß-Mo2C(001) surfaces.

The adsorption and activation of a CO2 molecule on cubic δ-MoC(001) and orthorhombic ß-Mo2C(001) surfaces have been investigated by means of periodic density functional theory based calculations using the Perdew-Burke-Ernzerhof exchange-correlation functional and explicitly accounting for (or neglecting) the dispersive force term description as proposed by Grimme. The DFT results indicate that an orthorhombic ß-Mo2C(001) Mo-terminated polar surface provokes the spontaneous cleavage of a C-O bond in CO2 and carbon monoxide formation, whereas on a ß-Mo2C(001) C-terminated polar surface or on a δ-MoC(001) nonpolar surface the CO2 molecule is activated yet the C-O bond prevails. Experimental tests showed that Mo-terminated ß-Mo2C(001) easily adsorbs and decomposes the CO2 molecule. This surface is an active catalyst for the hydrogenation of CO2 to methanol and methane. Although MoC does not dissociate C-O bonds on its own, it binds CO2 better than transition metal surfaces and is an active and selective catalyst for the CO2 + 3H2 → CH3OH + H2O reaction. Our theoretical and experimental results illustrate the tremendous impact that the carbon/metal ratio has on the chemical and catalytic properties of molybdenum carbides. This ratio must be taken into consideration when designing catalysts for the activation and conversion of CO2.

Density functional study of water-gas shift reaction on M3O(3x)/Cu(111).

Density functional theory (DFT) was employed to study the water dissociation and water-gas shift (WGS) reaction on a series of inverse model catalysts, M(3)O(3x)/Cu(111) (M = Mg, Ti, Zr, Mo, W; x = 1, 2, 3). It has been found that the WGS reaction on Cu can be facilitated by introducing various oxides to lower the barrier of water dissociation. Accordingly, the calculated reaction energy for water dissociation was used as a scaling descriptor to screen the WGS activity of oxide-Cu model catalysts. Our calculations show that the activity towards water dissociation decreases in a sequence: Mg(3)O(3)/Cu(111) > Zr(3)O(6)/Cu(111) > Ti(3)O(6)/Cu(111) > W(3)O(9)/Cu(111), Mo(3)O(9)/Cu(111). It seems that Mg(3)O(3)/Cu(111) is the best WGS catalyst among the systems studied here, being able to dissociate water with no barrier. During the process, both Cu and oxides participate in the reaction directly. The strong M(3)O(3x)-Cu interaction is able to tune the electronic structure of M(3)O(3x) and therefore the activity towards water dissociation. Further studies of the overall WGS reaction on Mg(3)O(3)/Cu(111) show that water dissociation may not be the key step to control the WGS reaction on Mg(3)O(3)/Cu(111) and the removal of H from Mg(3)O(3) can be problematic. The strong interaction between H and O from Mg(3)O(3) blocks the O sites for further water dissociation and therefore the WGS reaction. Our study observes a very different behavior of oxide clusters in such small size from the bigger ones supported on Cu(111) and provides new insight into the rational design of the WGS catalysts.

CO2 Activation and Methanol Synthesis on Novel Au/TiC and Cu/TiC Catalysts.

Small Cu and Au particles in contact with a TiC(001) surface undergo a charge polarization that makes them very active for CO2 activation and the catalytic synthesis of methanol. The binding energy of CO2 on these systems is in the range of 0.6 to 1.1 eV, much larger than those observed on surfaces or nanoparticles of Cu and Au. Thus, in spite of the poor CO2 hydrogenation performance of Cu(111) and Au(111), the Cu/TiC(001) and Au/TiC(001) systems display a catalytic activity for methanol synthesis substantially higher than that of conventional Cu/ZnO catalysts. The turnover frequencies for methanol production on Cu/TiC(001) are 170-500 times much larger than on Cu(111). The present study moves away from the typical approach of using metal/oxide catalysts for the synthesis of methanol via CO2 hydrogenation. This work shows that metal carbides can be excellent supports for enhancing the ability of noble metals to bond and activate CO2.

First-principles study of low Miller index Ni3S2 surfaces in hydrotreating conditions.

Density functional theory (DFT) calculations combined with surface thermodynamic arguments and the Gibbs-Curie-Wulff equilibrium morphology formalism have been employed to explore the effect of the reaction conditions, temperature (T), and gas-phase partial pressures (PH2 and PH2S) on the stability of nickel sulfide (Ni3S2) surfaces. Furthermore, the strength and nature of chemical bonds for selected Ni3S2 surface cuts were investigated with the quantum theory of atoms in molecules methodology. A particular analysis of the electrostatic potential within this theoretical framework is performed to study the potential activity of nickel sulfide nanoparticles as hydrodesulfurization (HDS) catalysts. The calculated thermodynamic surface stabilities and the resulting equilibrium morphology model suggest that unsupported Ni3S2 nanoparticles mainly expose (111) and (111) type surface faces in HDS conditions. Analysis of the electrostatic potential mapped onto a selected electron density isocontour (0.001 au) on those expose surface reveals a poor potential reactivity toward electron-donating reagents (i.e., low Lewis acidity). Consequently, a very low attraction between coordinatively unsaturated active sites (Lewis sites) exposed at the catalytic particles and the S atoms coming from reagent polluting molecules does inactive these kinds of particles for HDS.

Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice.

OBJECTIVE: Corticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: One hundred twenty-eight BALB/c mice (20-25 g). INTERVENTIONS: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 microg, ALIp) or intraperitoneally (125 microg, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALIexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). MEASUREMENTS AND MAIN RESULTS: At 24 hrs, lung static elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interleukin-6, and transforming growth factor (TGF)-beta levels in bronchoalveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta1 and TGF-beta2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFNgamma, and TGF-beta2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. CONCLUSIONS: Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Bench-to-bedside review: the role of glycosaminoglycans in respiratory disease.

The extracellular matrix (ECM) plays a significant role in the mechanical behaviour of the lung parenchyma. The ECM is composed of a three-dimensional fibre mesh that is filled with various macromolecules, among which are the glycosaminoglycans (GAGs). GAGs are long, linear and highly charged heterogeneous polysaccharides that are composed of a variable number of repeating disaccharide units. There are two main types of GAGs: nonsulphated GAG (hyaluronic acid) and sulphated GAGs (heparan sulphate and heparin, chondroitin sulphate, dermatan sulphate, and keratan sulphate). With the exception of hyaluronic acid, GAGs are usually covalently attached to a protein core, forming an overall structure that is referred to as proteoglycan. In the lungs, GAGs are distributed in the interstitium, in the sub-epithelial tissue and bronchial walls, and in airway secretions. GAGs have important functions in lung ECM: they regulate hydration and water homeostasis; they maintain structure and function; they modulate the inflammatory response; and they influence tissue repair and remodelling. Given the great diversity of GAG structures and the evidence that GAGs may have a protective effect against injury in various respiratory diseases, an understanding of changes in GAG expression that occur in disease may lead to opportunities to develop innovative and selective therapies in the future.

Respiratory changes in a murine model of spontaneous systemic lupus erythematosus.

The pathophysiology of systemic lupus erythematosus (SLE) has been very well described in many organs. However, the relation between extracellular matrix changes and lung dynamic mechanical behaviour deserves elucidation. To that end, pulmonary mechanics, lung morphometry and the amount of collagen and elastic fibres in the alveolar septa were analysed in mice with SLE [NZB/W (New Zealand Black/White) F1] and non-diseased NZW mice (control). Static (E(st)) and dynamic (E(dyn)) elastances, difference between dynamic and static elastances (DeltaE), airway resistance (R(aw)) and viscoelastic/inhomogeneous pressure (DeltaP(2)) were determined by the end-inflation occlusion method. Lungs were removed and prepared for histology. E(st), E(dyn), DeltaE and DeltaP(2) were higher in SLE than in control group, while R(aw) was similar in both groups. SLE group showed alveolar collapse and increased amount of elastic and collagen fibres. In conclusion, SLE mice showed an increase in elastic and viscoelastic/inhomogeneous pressures that was accompanied by deposition of collagen and elastic fibres in the alveolar septa.

Effect of corticosteroid on lung parenchyma remodeling at an early phase of acute lung injury.

In vivo (lung resistive and viscoelastic pressures and static elastance) and in vitro (tissue resistance, elastance, and hysteresivity) respiratory mechanics were analyzed 1 and 30 days after saline (control) or paraquat (P [10 and 25 mg/kg intraperitoneally]) injection in rats. Additionally, P10 and P25 were treated with methylprednisolone (2 mg/kg intravenously) at 1 or 6 hours after acute lung injury (ALI) induction. Collagen and elastic fibers were quantified. Lung resistive and viscoelastic pressures and static elastance were higher in P10 and P25 than in the control. Tissue elastance and resistance augmented from control to P10 (1 and 30 days) and P25. Hysteresivity increased in only P25. Methylprednisolone at 1 or 6 hours attenuated in vivo and in vitro mechanical changes in P25, whereas P10 parameters were similar to the control. Collagen increment was dose and time dependent. Elastic fibers increased in P25 and at 30 days in P10. Corticosteroid prevented collagen increment and avoided elastogenesis. In conclusion, methylprednisolone led to a complete maintenance of in vivo and in vitro respiratory mechanics in mild lesion, whereas it minimized the changes in tissue impedance and extracellular matrix in severe ALI. The beneficial effects of the early use of steroids in ALI remained unaltered at Day 30.

degS (hhoB) is an essential Escherichia coli gene whose indispensable function is to provide sigma (E) activity.

DegS (HhoB), a putative serine protease related to DegP/HtrA, regulates the basal and induced activity of the essential Escherichia coli sigma factor sigma (E), which is involved in the cellular response to extracytoplasmic stress. DegS promotes the destabilization of the sigma (E)-specific anti-sigma factor RseA, thereby releasing sigma (E) to direct gene expression. We demonstrate that degS is an essential E. coli gene and show that the essential function of DegS is to provide the cell with sigma (E) activity. We also show that the putative active site of DegS is periplasmic and that DegS requires its N-terminal transmembrane domain for its sigma (E)-related function.