Benralizumab in severe eosinophilic asthma: A real-world, single-center, observational study from Mexico

Introduction: Urbanization has increased the prevalence of asthma in lower- and middle-income countries. Severe eosinophilic asthma (SEA), a subtype of asthma, can be refractory to standard therapy. Biologics such as benralizumab target interleukin-5 and have demonstrated effectiveness in managing SEA. There exists no real-world evidence on the effectiveness of benralizumab in Mexico. Therefore, this study presents data on the role of benralizumab in managing SEA in Mexican patients. Objective: The effectiveness of benralizumab on the quality of life (QoL), asthma control, lung function, symptoms of asthma, and benralizumab’s safety profile were assessed. Methods: The study sample comprised 10 patients with SEA treated with a subcutaneous (SC) administration of benralizumab 30 mg once in 4 weeks for the first three doses followed by a dose every 8 weeks for 2 years. Laboratory tests, resting spirometry, and skin prick tests were conducted. Levels of fractional exhaled nitric oxide (FeNO) were evaluated, when possible, with the intent to phenotype asthma, as T2 high or non-T2, before starting benralizumab therapy. The Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were administered to evaluate the effectiveness of benralizumab on asthma control and QoL. Results: All patients showed significant symptom control, QoL, and lung function over 2 years. Mild adverse effects, such as headache and arthralgia, were observed. Conclusion: Benralizumab appears to be a promising agent in controlling SEA. This study has focused on measuring tangible outcomes, such as a reduction in symptoms, a reduction in exacerbation, and an improvement in QoL. Thus, benralizumab may constitute an important addition to the arsenal of medications against SEA (AU)

Exploring the stability of HEXACO-60 structure and the association of gender, age, and social position with personality traits across 18 countries.

OBJECTIVES: The present paper tests the cross-national stability of the HEXACO-60 structure across 18 countries from four continents. Gender and age differences across countries will be examined. Finally, this is the first study to explicitly analyze the relationships between the HEXACO and social position. METHOD: Ten thousand two hundred and ninety eight subjects (5,410 women and 4,888 men) from 18 countries and 13 languages were analyzed. Confirmatory factor analysis techniques were used to test configural, metric and scalar invariance models. Congruence coefficients with the original structure of the HEXACO-60 were computed for every culture. Effect sizes of gender, age, and social position factors across countries were also computed. RESULTS: HEXACO-60 demonstrates configural and metric invariance, but not scalar invariance. Congruence coefficients show a great equivalence in almost all countries and factors. Only Emotionality presents a large gender difference across countries. No relevant effect of age is observed. A profile of high scores on Honesty-Humility, Extraversion, Conscientiousness, and Openness to Experience, and low scores on Emotionality increases the likelihood of achieving a higher social position, although the effect sizes are small. CONCLUSIONS: HEXACO-60 is a useful instrument to conduct personality trait research and practice around the world. Implications of gender, social position, and country differences are discussed.

Multicultural Validation of the Zuckerman-Kuhlman-Aluja Personality Questionnaire Shortened Form (ZKA-PQ/SF) Across 18 Countries.

The aim of this study was to assess the psychometric properties of the Zuckerman-Kuhlman-Aluja Personality Questionnaire shortened form (ZKA-PQ/SF) in 18 cultures and 13 languages of different African, American, Asian, and European cultures and languages. The results showed that the five-factor structure with 20 facets replicated well across cultures with a total congruence coefficient of .97. A confirmatory factor analysis (CFA) resulted in adequate fit indices for the five factors based on the comparative fit index (CFI), Tucker-Lewis index (TLI; >.90), and RMSEA (.031-.081). A series of CFA to assess measurement invariance across cultures resulted in adequate CFIs and TLIs for configural and metric invariance. However, factors did not show scalar invariance. Alpha internal consistencies of five factors ranged between .77 (Sensation Seeking) and .86 (Neuroticism). The average alpha of the 20 facets was .64 with a range from .43 (SS4) to .75 (AG1). Nevertheless, alpha reliabilities were lower in some facets and cultures, especially for Senegal and Togo. The average percentage of the variance explained based on the adjusted R2 was 2.9%, 1.7%, and 5.1% for age, sex, and, cultures, respectively. Finally, multidimensional scaling suggested that geographically or culturally close cultures share mean profile similarities.

Jitterbug/Filamin and Myosin-II form a complex in tendon cells required to maintain epithelial shape and polarity during musculoskeletal system development.

During musculoskeletal system development, mechanical tension is generated between muscles and tendon-cells. This tension is required for muscle differentiation and is counterbalanced by tendon-cells avoiding tissue deformation. Both, Jbug/Filamin, an actin-meshwork organizing protein, and non-muscle Myosin-II (Myo-II) are required to maintain the shape and cell orientation of the Drosophila notum epithelium during flight muscle attachment to tendon cells. Here we show that halving the genetic dose of Rho kinase (Drok), the main activator of Myosin-II, enhances the epithelial deformation and bristle orientation defects associated with jbug/Filamin knockdown. Drok and activated Myo-II localize at the apical cell junctions, tendon processes and are associated to the myotendinous junction. Further, we found that Jbug/Filamin co-distribute at tendon cells with activated Myo-II. Finally, we found that Jbug/Filamin and Myo-II are in the same molecular complex and that the actin-binding domain of Jbug/Filamin is necessary for this interaction. These data together suggest that Jbug/Filamin and Myo-II proteins may act together in tendon cells to balance the tension generated during development of muscles-tendon interaction, maintaining the shape and polarity of the Drosophila notum epithelium.

Mechanical Control of Myotendinous Junction Formation and Tendon Differentiation during Development.

The development of the musculoskeletal system is a great model to study the interplay between chemical and mechanical inter-tissue signaling in cell adhesion, tissue morphogenesis and differentiation. In both vertebrates and invertebrates (e.g., Drosophila melanogaster) the formation of muscle-tendon interaction generates mechanical forces which are required for myotendinous junction maturation and tissue differentiation. In addition, these forces must be withstood by muscles and tendons in order to prevent detachment from each other, deformation or even losing their integrity. Extracellular matrix remodeling at the myotendinous junction is key to resist mechanical load generated by muscle contraction. Recent evidences in vertebrates indicate that mechanical forces generated during junction formation regulate chemical signaling leading to extracellular matrix remodeling, however, the mechanotransduction mechanisms associated to this response remains elusive. In addition to extracellular matrix remodeling, the ability of Drosophila tendon-cells to bear mechanical load depends on rearrangement of tendon cell cytoskeleton, thus studying the molecular mechanisms involved in this process is critical to understand the contribution of mechanical forces to the development of the musculoskeletal system. Here, we review recent findings regarding the role of chemical and mechanical signaling in myotendinous junction formation and tendon differentiation, and discuss molecular mechanisms of mechanotransduction that may allow tendon cells to withstand mechanical load during development of the musculoskeletal system.

Establishment of the Muscle-Tendon Junction During Thorax Morphogenesis in Drosophila Requires the Rho-Kinase.

The assembly of the musculoskeletal system in Drosophila relies on the integration of chemical and mechanical signaling between the developing muscles with ectodermal cells specialized as "tendon cells." Mechanical tension generated at the junction of flight muscles and tendon cells of the notum epithelium is required for muscle morphogenesis, and is balanced by the epithelium in order to not deform. We report that Drosophila Rho kinase (DRok) is necessary in tendon cells to assemble stable myotendinous junctions (MTJ), which are required for muscle morphogenesis and survival. In addition, DRok is required in tendon cells to maintain epithelial shape and cell orientation in the notum, independently of chascon (chas). Loss of DRok function in tendon cells results in mis-orientation of tendon cell extensions and abnormal accumulation of Thrombospondin and ßPS-integrin, which may cause abnormal myotendinous junction formation and muscle morphogenesis. This role does not depend exclusively on nonmuscular Myosin-II activation (Myo-II), indicating that other DRok targets are key in this process. We propose that DRok function in tendon cells is key to promote the establishment of MTJ attachment and to balance mechanical tension generated at the MTJ by muscle compaction.