EMT activates exocytotic Rabs to coordinate invasion and immunosuppression in lung cancer.

Epithelial-to-mesenchymal transition (EMT) underlies immunosuppression, drug resistance, and metastasis in epithelial malignancies. However, the way in which EMT orchestrates disparate biological processes remains unclear. Here, we identify an EMT-activated vesicular trafficking network that coordinates promigratory focal adhesion dynamics with an immunosuppressive secretory program in lung adenocarcinoma (LUAD). The EMT-activating transcription factor ZEB1 drives exocytotic vesicular trafficking by relieving Rab6A, Rab8A, and guanine nucleotide exchange factors from miR-148a-dependent silencing, thereby facilitating MMP14-dependent focal adhesion turnover in LUAD cells and autotaxin-mediated CD8+ T cell exhaustion, indicating that cell-intrinsic and extrinsic processes are linked through a microRNA that coordinates vesicular trafficking networks. Blockade of ZEB1-dependent secretion reactivates antitumor immunity and negates resistance to PD-L1 immune checkpoint blockade, an important clinical problem in LUAD. Thus, EMT activates exocytotic Rabs to drive a secretory program that promotes invasion and immunosuppression in LUAD.

Time-resolved structure-function coupling in brain networks.

The relationship between structural and functional connectivity in the brain is a key question in systems neuroscience. Modern accounts assume a single global structure-function relationship that persists over time. Here we study structure-function coupling from a dynamic perspective, and show that it is regionally heterogeneous. We use a temporal unwrapping procedure to identify moment-to-moment co-fluctuations in neural activity, and reconstruct time-resolved structure-function coupling patterns. We find that patterns of dynamic structure-function coupling are region-specific. We observe stable coupling in unimodal and transmodal cortex, and dynamic coupling in intermediate regions, particularly in insular cortex (salience network) and frontal eye fields (dorsal attention network). Finally, we show that the variability of a region's structure-function coupling is related to the distribution of its connection lengths. Collectively, our findings provide a way to study structure-function relationships from a dynamic perspective.

Improving cardiovascular magnetic resonance access in low- and middle-income countries for cardiomyopathy assessment: rapid cardiovascular magnetic resonance.

AIMS: To evaluate the impact of a simplified, rapid cardiovascular magnetic resonance (CMR) protocol embedded in care and supported by a partner education programme on the management of cardiomyopathy (CMP) in low- and middle-income countries (LMICs). METHODS AND RESULTS: Rapid CMR focused particularly on CMP was implemented in 11 centres, 7 cities, 5 countries, and 3 continents linked to training courses for local professionals. Patients were followed up for 24 months to assess impact. The rate of subsequent adoption was tracked. Five CMR conferences were delivered (920 attendees-potential referrers, radiographers, reporting cardiologists, or radiologists) and five new centres starting CMR. Six hundred and one patients were scanned. Cardiovascular magnetic resonance indications were 24% non-contrast T2* scans [myocardial iron overload (MIO)] and 72% suspected/known cardiomyopathies (including ischaemic and viability). Ninety-eighty per cent of studies were of diagnostic quality. The average scan time was 22 ± 6 min (contrast) and 12 ± 4 min (non-contrast), a potential cost/throughput reduction of between 30 and 60%. Cardiovascular magnetic resonance findings impacted management in 62%, including a new diagnosis in 22% and MIO detected in 30% of non-contrast scans. Nine centres continued using rapid CMR 2 years later (typically 1-2 days per week, 30 min slots). CONCLUSIONS: Rapid CMR of diagnostic quality can be delivered using available technology in LMICs. When embedded in care and a training programme, costs are lower, care is improved, and services can be sustained over time.

Family functioning and school connectivity in Mexican high school adolescents / Funcionamento familiar e conectividade escolar em adolescentes mexicanos do Ensino Médio

Family functionality has shown its relevance in the comprehensive development of adolescents, with school connectivity being a very important aspect. To determine the association between family functioning and school connectivity in Mexican high school adolescents, an analytical cross-sectional study was carried out in a census of 396 adolescents in a public high school in Mexico. The self-report of family functioning and the school connectedness scale were used, both with α > 0.84. ꭕ2 and ANOVA were applied. The results show significant differences in conflict with shift (morning ꭕ2 = 42.47 vs. evening ꭕ2 = 40.35, F = 4.57, p = 0.033), and leadership with degree (1st ꭕ2 = 8.14, 2nd ꭕ2 = 8.97, 3rd ꭕ2 = 8.90, F = 3.52, p = 0.030). Connectivity associated with school variables (p < 0.05). There are no differences or association between sex, age or qualifications with connectivity. Family functioning was associated in affective expression with school (ꭕ2 = 3.77, p = 0.055) and in leadership with students (ꭕ2 = 2.92, p = 0.05). It is concluded that the leadership of the parents and the affective expression of the family favors school connectivity between students and with their school.

A funcionalidade familiar tem mostrado sua relevância no desenvolvimento integral dos adolescentes, sendo a conectividade escolar um aspecto muito importante. Para determinar a associação entre funcionamento familiar e conectividade escolar em adolescentes mexicanos do Ensino Médio, foi realizado um estudo transversal analítico em um censo de 396 adolescentes em uma escola pública no México. Foram utilizados o autorrelato de funcionamento familiar e a escala de conectividade escolar, ambos com α > 0,84. ꭕ2 e ANOVA foram aplicados. Os resultados mostram diferenças significativas no conflito com turno (ꭕ2 da manhã = 42,47 vs. ꭕ2 da noite = 40,35, F = 4,57, p = 0,033) e liderança com grau (1º ꭕ2 = 8,14, 2º ꭕ2 = 8,97, 3º ꭕ2 = 8,90, F = 3,52, p = 0,030). Conectividade associada a variáveis escolares (p < 0,05). Não há diferenças ou associação entre sexo, idade ou qualificações com conectividade. O funcionamento familiar foi associado na expressão afetiva com a escola (ꭕ2 = 3,77, p = 0,055) e na liderança com os alunos (ꭕ2 = 2,92, p = 0,05). Conclui-se que a liderança dos pais e a expressão afetiva da família favorece a conectividade escolar entre os alunos e com sua escola.

Chest computed tomography findings associated with severity and mortality in patients with COVID-19. / Hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19.

OBJECTIVES: To determine chest CT findings associated with severity and mortality in patients with COVID-19 from the Hospital Nacional Edgardo Rebagliati Martins (HNERM) and propose cut-off values for a tomographic severity score (TSS). MATERIALS AND METHODS: A retrospective cohort study was conducted in 254 patients with COVID-19 who underwent chest CT as part of their initial evaluation at the emergency room; they were classified according to clinical severity. Main tomographic findings were described. A multivariate analysis with logistic regression was carried out to determine association with clinical severity, the Cox model was used to evaluate mortality, and ROC curves were elaborated to assess cutoff values for the TSS. RESULTS: CT findings associated with clinical severity were the following: diffuse pattern (OR: 3.23, 95% CI: 1.46-7.14), crazy-paving pattern (OR: 2.48; 95% CI: 1.08-5.68), and high TSS value (OR: 1.73; 95% CI: 1.49-2.02). The crazy-paving pattern (HR: 1.78; 95% CI: 1.03-3.06) and a high TSS value (HR: 1.33; 95% CI: 1.20-1.48) were found to be associated with mortality. A value of 7 in the TSS showed a sensibility of 94.4% and a specificity of 100% for moderate disease, and a value of 13 showed a sensibility of 84.9% and a specificity of 70.6% for severe disease. CONCLUSIONS: The diffuse pattern is associated with higher clinical severity. The crazy-paving pattern and a high TSS value are associated with higher clinical severity and mortality. We propose TSS cutoff values of 7 and 13 for moderate and severe disease, respectively.

OBJETIVOS: Determinar los hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19 del Hospital Nacional Edgardo Rebagliati Martins (HNERM), y proponer puntos de corte para una puntuación tomográfica de severidad (PTS). MATERIALES Y MÉTODOS: Estudio de cohorte retrospectivo en 254 pacientes con la COVID-19 que contaban con tomografía de tórax clasificada según severidad clínica. Se realizó un análisis multivariado mediante regresión logística para determinar asociación con la severidad clínica, un análisis de regresión de Cox para evaluar mortalidad, y curvas ROC para evaluar la PTS. RESULTADOS: Los hallazgos tomográficos asociados a severidad clínica fueron el patrón difuso de las lesiones (OR: 3,23, IC 95%: 1,46-7,14), patrón en «empedrado¼ (OR: 2,48; IC 95%: 1,08-5,68) y mayor valor en la PTS (OR: 1,73; IC 95%: 1,49-2,02). Los hallazgos asociados a mortalidad fueron el patrón en «empedrado¼ (HR: 1,78; IC 95%: 1,03-3,06) y mayor valor en la PTS (HR: 1,33; IC 95%: 1,20-1,48). Un valor de 7 en la PTS tuvo una sensibilidad de 94,4% y especificidad de 100% para identificar casos moderados y un valor de 13 tuvo una sensibilidad de 84,9% y una especificidad de 70,6% para casos severos. CONCLUSIONES: El patrón difuso de las lesiones se asoció a una mayor severidad clínica. El patrón en «empedrado¼ y un mayor valor en la PTS se asociaron a mayor severidad clínica y a mortalidad. Se proponen los valores de 7 y 13 como puntos de corte de la PTS para identificar casos moderados y severos.

Hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19

Objetivos: Determinar los hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19 del Hospital Nacional Edgardo Rebagliati Martins (HNERM), y proponer puntos de corte para una puntuación tomográfica de severidad (PTS). Materiales y métodos: Estudio de cohorte retrospectivo en 254 pacientes con la COVID-19 que contaban con tomografía de tórax clasificada según severidad clínica. Se realizó un análisis multivariado mediante regresión logística para determinar asociación con la severidad clínica, un análisis de regresión de Cox para evaluar mortalidad, y curvas ROC para evaluar la PTS. Resultados: Los hallazgos tomográficos asociados a severidad clínica fueron el patrón difuso de las lesiones (OR: 3,23, IC 95%: 1,46-7,14), patrón en «empedrado» (OR: 2,48; IC 95%: 1,08-5,68) y mayor valor en la PTS (OR: 1,73; IC 95%: 1,49-2,02). Los hallazgos asociados a mortalidad fueron el patrón en «empedrado» (HR: 1,78; IC 95%: 1,03-3,06) y mayor valor en la PTS (HR: 1,33; IC 95%: 1,20-1,48). Un valor de 7 en la PTS tuvo una sensibilidad de 94,4% y especificidad de 100% para identificar casos moderados y un valor de 13 tuvo una sensibilidad de 84,9% y una especificidad de 70,6% para casos severos. Conclusiones: El patrón difuso de las lesiones se asoció a una mayor severidad clínica. El patrón en «empedrado» y un mayor valor en la PTS se asociaron a mayor severidad clínica y a mortalidad. Se proponen los valores de 7 y 13 como puntos de corte de la PTS para identificar casos moderados y severos.

Objectives: To determine chest CT findings associated with severity and mortality in patients with COVID-19 from the Hospital Nacional Edgardo Rebagliati Martins (HNERM) and propose cut-off values for a tomographic severity score (TSS). Materials and Methods: A retrospective cohort study was conducted in 254 patients with COVID-19 who underwent chest CT as part of their initial evaluation at the emergency room; they were classified according to clinical severity. Main tomographic findings were described. A multivariate analysis with logistic regression was carried out to determine association with clinical severity, the Cox model was used to evaluate mortality, and ROC curves were elaborated to assess cutoff values for the TSS. Results: CT findings associated with clinical severity were the following: diffuse pattern (OR: 3.23, 95% CI: 1.46-7.14), crazy-paving pattern (OR: 2.48; 95% CI: 1.08-5.68), and high TSS value (OR: 1.73; 95% CI: 1.49-2.02). The crazy-paving pattern (HR: 1.78; 95% CI: 1.03-3.06) and a high TSS value (HR: 1.33; 95% CI: 1.20-1.48) were found to be associated with mortality. A value of 7 in the TSS showed a sensibility of 94.4% and a specificity of 100% for moderate disease, and a value of 13 showed a sensibility of 84.9% and a specificity of 70.6% for severe disease. Conclusions: The diffuse pattern is associated with higher clinical severity. The crazy-paving pattern and a high TSS value are associated with higher clinical severity and mortality. We propose TSS cutoff values of 7 and 13 for moderate and severe disease, respectively.

Signal propagation via cortical hierarchies.

The wiring of the brain is organized around a putative unimodal-transmodal hierarchy. Here we investigate how this intrinsic hierarchical organization of the brain shapes the transmission of information among regions. The hierarchical positioning of individual regions was quantified by applying diffusion map embedding to resting-state functional MRI networks. Structural networks were reconstructed from diffusion spectrum imaging and topological shortest paths among all brain regions were computed. Sequences of nodes encountered along a path were then labeled by their hierarchical position, tracing out path motifs. We find that the cortical hierarchy guides communication in the network. Specifically, nodes are more likely to forward signals to nodes closer in the hierarchy and cover a range of unimodal and transmodal regions, potentially enriching or diversifying signals en route. We also find evidence of systematic detours, particularly in attention networks, where communication is rerouted. Altogether, the present work highlights how the cortical hierarchy shapes signal exchange and imparts behaviorally relevant communication patterns in brain networks.

Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8+ T cell exhaustion.

Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic and RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated collagen correlates with decreased total CD8+ T cells and increased exhausted CD8+ T cell subpopulations in murine and human lung tumors. Collagen-induced T cell exhaustion occurs through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1. Reduction in tumor collagen deposition through LOXL2 suppression increases T cell infiltration, diminishes exhausted T cells, and abrogates resistance to anti-PD-L1. Abrogating LAIR1 immunosuppression through LAIR2 overexpression or SHP-1 inhibition sensitizes resistant lung tumors to anti-PD-1. Clinically, increased collagen, LAIR1, and TIM-3 expression in melanoma patients treated with PD-1 blockade predict poorer survival and response. Our study identifies collagen and LAIR1 as potential markers for immunotherapy resistance and validates multiple promising therapeutic combinations.

Elementos que configuran la percepción de seguridad escolar en estudiantes de secundaria / Elements that configure school safety perception in high school students

Resumen El objetivo de este trabajo fue describir los elementos que configuran la percepción de seguridad escolar en estudiantes de secundaria. Se presenta un estudio cualitativo con enfoque sistémico ecológico. Por medio de un muestreo teórico, se incluyeron a 22 estudiantes, 50 % hombres con 12 a 16 años, quienes participaron en un grupo focal, previo consentimiento informado de los padres. Los datos recabados fueron audio grabados; se transcribieron y analizaron con el método de análisis de contenido por medio del programa Maxqda 18. Se identificaron 4 categorías que configuran la percepción de seguridad escolar: 1) condiciones de la escuela (físicas y organizacionales); 2) elementos relacionados con los maestros; 3) elementos relacionados con los compañeros, y 4) elementos relacionados con los padres. Los hallazgos sugieren que las condiciones físicas y organizacionales mantienen un papel importante en la con figuración del sentido de seguridad escolar. Asimismo, la cercanía y apoyo recibido de actores del contexto (maestros, padres y alumnos) promueve una percepción más positiva de la seguridad.

Abstract The aim of this study was to describe the individual elements that configure the school safety perception in middle school students. We designed a qualitative study, with a systemic and ecological approach. Using a theoretical sampling, we included 22 students, 50% man with an age from 12 to 16 years old, who participated in a focus group, previous informed consent from the parents. The session was videotaped, the data was transcribed and analyzed using content analysis with the program MAXQDA 18. We identified four categories of factors that configure the student's school safety perception: 1) school conditions (physical and organizational); 2) elements related to teachers; 3) elements related to peers; and 4) elements related to parents. The findings suggest that the school´s physical and organizational conditions have an important role in the configuration of the school safety perception. Likewise, the closeness and support received by actors from the school context (teachers, parents and peers) favor a more positive perception of school safety.

STING Pathway Expression Identifies NSCLC With an Immune-Responsive Phenotype.

INTRODUCTION: Although the combination of anti-programmed cell death-1 or anti-programmed cell death ligand-1 (PD-L1) with platinum chemotherapy is a standard of care for NSCLC, clinical responses vary. Even though predictive biomarkers (which include PD-L1 expression, tumor mutational burden, and inflamed immune microenvironment) are validated for immunotherapy, their relevance to chemoimmunotherapy combinations is less clear. We have recently reported that activation of the stimulator of interferon genes (STING) innate immune pathway enhances immunotherapy response in SCLC. Here, we hypothesize that STING pathway activation may predict and underlie predictive correlates of antitumor immunity in NSCLC. METHODS: We analyzed transcriptomic and proteomic profiles in two NSCLC cohorts from our institution (treatment-naive patients in the Profiling of Resistance Patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax study and relapsed patients in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination study) and The Cancer Genome Atlas (N = 1320). Tumors were stratified by STING activation on the basis of protein or mRNA expression of cyclic GMP-AMP synthase, phospho-STING, and STING-mediated chemokines (chemokine ligand 5 [CCL5] and C-X-C motif chemokine 10 [CXCL10]). STING activation in patient tumors and in platinum-treated preclinical NSCLC models was correlated with biomarkers of immunotherapy response. RESULTS: STING activation is associated with higher levels of intrinsic DNA damage, targetable immune checkpoints, and chemokines in treatment-naive and relapsed lung adenocarcinoma. We observed that tumors with lower STING and immune gene expression show higher frequency of serine-threonine kinase 11 (STK11) mutations; however, we identified a subset of these tumors that are TP53 comutated and display high immune- and STING-related gene expression. Treatment with cisplatin increases STING pathway activation and PD-L1 expression in multiple NSCLC preclinical models, including adeno- and squamous cell carcinoma. CONCLUSIONS: STING pathway activation in NSCLC predicts features of immunotherapy response and is enhanced by cisplatin treatment. This suggests a possible predictive biomarker and mechanism for improved response to chemoimmunotherapy combinations.

Gradients of structure-function tethering across neocortex.

The white matter architecture of the brain imparts a distinct signature on neuronal coactivation patterns. Interregional projections promote synchrony among distant neuronal populations, giving rise to richly patterned functional networks. A variety of statistical, communication, and biophysical models have been proposed to study the relationship between brain structure and function, but the link is not yet known. In the present report we seek to relate the structural and functional connection profiles of individual brain areas. We apply a simple multilinear model that incorporates information about spatial proximity, routing, and diffusion between brain regions to predict their functional connectivity. We find that structure-function relationships vary markedly across the neocortex. Structure and function correspond closely in unimodal, primary sensory, and motor regions, but diverge in transmodal cortex, particularly the default mode and salience networks. The divergence between structure and function systematically follows functional and cytoarchitectonic hierarchies. Altogether, the present results demonstrate that structural and functional networks do not align uniformly across the brain, but gradually uncouple in higher-order polysensory areas.

La digitopuntura como alternativa de rehabilitación en pacientes con parálisis facial / Digitopuncture as rehabilitation alternative in patients with facial paralysis

Introducción: Una de las secuelas más recurrentes de la rama neurológica es la parálisis facial, que no solo afecta al área motora, sino también a la psicológica, por ser el rostro la imagen representativa de la persona. Objetivo: Evaluar la influencia de la digitopuntura como alternativa terapéutica en pacientes con parálisis facial, mediante la aplicación de la técnica fotográfica para la medición de ángulos según los indicadores de evaluación propuestos. Métodos: Se efectuó un estudio experimental y longitudinal de tipo panel, con un pretest y un postest, en el Servicio de Fisioterapia del Hospital Clínico-Quirúrgico Militar Central Dr. Carlos Juan Finlay, en el municipio de Marianao, La Habana, de mayo a julio del 2016, para lo cual se conformaron dos grupos: uno de control, en el cual se aplicó tratamiento convencional (masaje, ejercicios de la mímica y agentes físicos), y otro de experimento, que recibió digitopuntura adicionada al masaje. Resultados: En la evaluación de ambos grupos, se obtuvo que en el de control los mejores resultados figuraron en el eje central de la boca, seguido de la contracción muscular, mientras que en el grupo de experimento el total mostró notables cambios en todos los indicadores, con predominio de la contracción muscular. Al comparar los resultados de ambos grupos en el pretest y el postest, se evidenció la incidencia y efectividad de la digitopuntura en el grupo de experimento. Conclusiones: La digitopuntura, como parte de la rehabilitación en personas afectadas por parálisis facial, influyó en una mejor recuperación y disminuyó considerablemente el tiempo de tratamiento, lo que incidió mayormente en las féminas.

Introduction: One of the most recurrent sequels in the neurological branch is the facial paralysis which not only affects the motor area, but also the psychological one, as the face is the person's representative image. Objective: To evaluate the influence of digitopuncture as therapeutic alternative in patients with facial paralysis, by using the photographic technique for measuring angles according to the proposed evaluation indicators. Methods: A panel experimental and longitudinal study was made, with a pretest and a posttest, in the Physiotherapy Service of Dr. Carlos Juan Finlay Hospital Central Military Clinical-surgical, in Marianao municipality, Havana, from May to July, 2016, for which two groups were formed: a control group, in which conventional treatment was applied (massage, exercises of the pantomime and physical agents), and an experiment group which received digitopuncture besides massage. Results: In the evaluation of both groups, it was obtained that in the control group the best results were in the central axis of the mouth, followed by the muscle contraction, while the whole experimental group showed remarkable changes in all the indicators, with prevalence of the muscle contraction. When comparing the results of both groups in the pretest and posttest, the incidence and effectiveness of the digitopuncture was evidenced in the experimental group. Conclusions: Digitopuncture, as part of the rehabilitation in patients affected due to facial paralysis, influenced in a better recovery and decreased the time of treatment considerably, which had a higher incidence in the female group.

INCA (Peru) Study: Impact of Non-Invasive Cardiac Magnetic Resonance Assessment in the Developing World.

Background Advanced cardiac imaging permits optimal targeting of cardiac treatment but needs to be faster, cheaper, and easier for global delivery. We aimed to pilot rapid cardiac magnetic resonance ( CMR ) with contrast in a developing nation, embedding it within clinical care along with training and mentoring. Methods and Results A cross-sectional study of CMR delivery and clinical impact assessment performed 2016-2017 in an upper middle-income country. An International partnership (clinicians in Peru and collaborators from the United Kingdom, United States, Brazil, and Colombia) developed and tested a 15-minute CMR protocol in the United Kingdom, for cardiac volumes, function and scar, and delivered it with reporting combined with training, education and mentoring in 2 centers in the capital city, Lima, Peru, 100 patients referred by local doctors from 6 centers. Management changes related to the CMR were reviewed at 12 months. One-hundred scans were conducted in 98 patients with no complications. Final diagnoses were cardiomyopathy (hypertrophic, 26%; dilated, 22%; ischemic, 15%) and 12 other pathologies including tumors, congenital heart disease, iron overload, amyloidosis, genetic syndromes, vasculitis, thrombi, and valve disease. Scan cost was $150 USD, and the average scan duration was 18±7 minutes. Findings impacted management in 56% of patients, including previously unsuspected diagnoses in 19% and therapeutic management changes in 37%. Conclusions Advanced cardiac diagnostics, here CMR with contrast, is possible using existing infrastructure in the developing world in 18 minutes for $150, resulting in important changes in patient care.

Stochastic resonance at criticality in a network model of the human cortex.

Stochastic resonance is a phenomenon in which noise enhances the response of a system to an input signal. The brain is an example of a system that has to detect and transmit signals in a noisy environment, suggesting that it is a good candidate to take advantage of stochastic resonance. In this work, we aim to identify the optimal levels of noise that promote signal transmission through a simple network model of the human brain. Specifically, using a dynamic model implemented on an anatomical brain network (connectome), we investigate the similarity between an input signal and a signal that has traveled across the network while the system is subject to different noise levels. We find that non-zero levels of noise enhance the similarity between the input signal and the signal that has traveled through the system. The optimal noise level is not unique; rather, there is a set of parameter values at which the information is transmitted with greater precision, this set corresponds to the parameter values that place the system in a critical regime. The multiplicity of critical points in our model allows it to adapt to different noise situations and remain at criticality.

[Representation of self-care of health at work among urban bus drivers in Guadalajara, Mexico]. / Representación del autocuidado de la salud en el trabajo de conductores de autobús urbano de Guadalajara, México.

This study aimed to analyze the social representations of health self-care at work among urban bus drivers in Guadalajara, Mexico. The methodology was qualitative, with a multi-method design based on the theory of social representations. The first stage involved active observation sessions with the information recorded in field notes; in the second stage, the associative letter technique and successively hierarchized trees technique were applied to 20 drivers, submitting the data to a classical analysis of the free associations; a third stage involved semi-structured interviews with 4 drivers, submitted to content analysis. The results indicate that structurally, the representation is centered on alimentation, presenting the concepts rest and corrective health care at peripheral levels. Procedurally, the represeentation centers in the psychosocial factors derived from the working conditions, while the rest of the work characteristics are seen as low risk to health. The self-care actions mentioned by the participants only focus on the workinging conditions perceived as risky. The social representation of health self-care at work is a collective mental construction, developed and modified through social interactions, which influences self-care measures used against the risks perceived in the workplace.

Representación del autocuidado de la salud en el trabajo de conductores de autobús urbano de Guadalajara, México / Representation of self-care of health at work among urban bus drivers in Guadalajara, Mexico / Representação do autocuidado da saúde no trabalho de motoristas de ônibus urbano em Guadalajara, México

Resumen: El objetivo del estudio fue analizar las representaciones sociales del autocuidado de la salud en el trabajo en conductores de autobús urbano de Guadalajara, México. La metodología fue cualitativa, con un diseño multimétodo, basado en la teoría de las representaciones sociales. En una primera etapa se efectuaron sesiones de observación participante, la información se registró en notas de campo; en una segunda fase se aplicaron las técnicas de la carta asociativa y los tris jerarquizados sucesivos a 20 conductores, los datos se sometieron a análisis clásico de las asociaciones libres; en una tercera etapa se realizaron entrevistas semi-estructuradas a 4 conductores, siendo sometidas a análisis de contenido. Los resultados indican que, estructuralmente, la representación se centra en la alimentación, presentándose en niveles periféricos el descanso y el cuidado correctivo de la salud. Procesualmente, la representación gira en torno a los factores psicosociales que se desprenden de las condiciones de trabajo, el resto de las características del ejercicio laboral se consideran poco riesgosas para la salud. Las acciones de autocuidado mencionadas se enfocan en las condiciones de trabajo percibidas como riesgosas. La representación social del autocuidado de la salud en el trabajo es una construcción mental colectiva, desarrollada y modificada a través de la interacción social, la cual influye en las acciones de autocuidado empleadas frente a los riesgos existentes en el entorno laboral.

Abstract: This study aimed to analyze the social representations of health self-care at work among urban bus drivers in Guadalajara, Mexico. The methodology was qualitative, with a multi-method design based on the theory of social representations. The first stage involved active observation sessions with the information recorded in field notes; in the second stage, the associative letter technique and successively hierarchized trees technique were applied to 20 drivers, submitting the data to a classical analysis of the free associations; a third stage involved semi-structured interviews with 4 drivers, submitted to content analysis. The results indicate that structurally, the representation is centered on alimentation, presenting the concepts rest and corrective health care at peripheral levels. Procedurally, the represeentation centers in the psychosocial factors derived from the working conditions, while the rest of the work characteristics are seen as low risk to health. The self-care actions mentioned by the participants only focus on the workinging conditions perceived as risky. The social representation of health self-care at work is a collective mental construction, developed and modified through social interactions, which influences self-care measures used against the risks perceived in the workplace.

Resumo: O objetivo deste estudo foi analisar as representações sociais do autocuidado da saúde no trabalho dos motoristas de ônibus urbano de Guadalajara, México. A metodologia foi qualitativa, com uma abordagem multimétodo, baseada na teoria das representações sociais. Em uma primeira etapa foram efetuadas sessões de observação participante, a informação foi registrada em anotações de campo; na segunda fase foram aplicadas técnicas de cartas associativas e momentos hierárquicos sucessivos a 20 motoristas, cujos dados foram submetidos à análise clássico das associações livres; em uma terceira etapa foram realizadas entrevistas semiestruturadas a quatro motoristas, sendo submetidas a análises de conteúdo. Os resultados indicam que, estruturalmente, a representação está focada na alimentação, apresentando-se em níveis periféricos o descanso, junto com o cuidado correto da saúde. Processualmente, a representação vira em torno dos fatores psicossociais, que se desprendem das condições de trabalho, o resto das características da atividade laboral foi considerado pouco arriscado para a saúde. As ações de autocuidado citadas foram focadas às condições de trabalho percebidas como arriscadas. A representação social do autocuidado da saúde no trabalho é uma construção mental coletiva, desenvolvida e modificada através da interação social, a qual influencia as ações de autocuidado empregadas frente aos riscos existentes no entorno laboral.

Azide-enolate 1,3-dipolar cycloaddition in the synthesis of novel triazole-based miconazole analogues as promising antifungal agents.

Seven miconazole analogs involving 1,4,5-tri and 1,5-disubstituted triazole moieties were synthesized by azide-enolate 1,3-dipolar cycloaddition. The antifungal activity of these compounds was evaluated in vitro against four filamentous fungi, including Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae, and Mucor hiemalis as well as three species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 4b, 4d and 7b can be considered as drug candidates for future complementary biological studies due to their good/excellent antifungal activities.

A facile synthesis of novel miconazole analogues and the evaluation of their antifungal activity.

Four novel miconazole analogues (8-11) were synthetized and evaluated for activity against four filamentous fungi (Mucor hiemalis, Aspergillus fumigatus, Trichosporon cutaneum, and Rhizopus oryzae) and eight species of Candida as yeast specimens. Compounds 9 and 10 showed very good activity when evaluated in yeast (MIC 0.112 and 0.163 µg/mL) compared to the reference compound, itraconazole (MIC 0.067 µg/mL). The best antifungal activity in filamentous strains was shown by compound 9. Hence compounds 9 and 10 represent new leads for further pharmacomodulation in this series.

Tumor necrosis factor alpha -238 G/A and -308 G/A polymorphisms and soluble TNF-α levels in chronic kidney disease: correlation with clinical variables.

Chronic kidney disease (CKD) is characterized by accumulation of proinflammatory cytokines, mainly tumor necrosis factor alpha (TNF-α). Single nucleotide polymorphisms (SNPs) of TNFA gene, including -238 G/A and -308 G/A, have been associated with alteration in the soluble TNF-α (sTNF-α) expression. The aim was to investigate the association of -238 y -308 TNFA gene SNPs with sTNF-α levels in CKD patients. We included 150 CKD patients and 192 control subjects (CS). Both SNPs were genotyped with polymerase chain reaction-restriction fragment length polymorphism technique and sTNF-α levels were measured by enzyme-linked immunosorbent assay. The genotypic distribution of -238 and -308 SNPs was not significantly different between CKD patients and CS (p > 0.001). However, the sTNF-α levels were higher in CKD, compared to CS (p < 0.001). Also, sTNF-α correlated with creatinine (r = 0.279, p = 0.004), urea (r = 0.325, p = 0.001), phosphorus (r = 0.479, p = 0.001), glomerular filtration rate (r = -0.236, p = 0.019) and monocyte count (r = 0.276, p = 0.010). In conclusion, elevated sTNF-α levels are associated with CKD. However, the -238 and -308 TNFA gene SNPs were not associated with susceptibility to CKD and sTNF-α levels in a Mexican population.

Association of genetic polymorphisms with histological grading of necroinflammation, staging of fibrosis, and liver function in Mexicans with chronic hepatitis C virus infection.

BACKGROUND/AIM: The aim of this work was to establish an association between the single-nucleotide polymorphisms (SNPs) of TGFB1 (rs1800471), AT (rs3789679), MMP-1 (rs17886084), MMP-3 (rs35068180), and PAI-1 (rs1799889) and the histological grading of necroinflammation, staging of hepatic fibrosis, and liver function in Mexican patients with advanced liver fibrosis due to chronic hepatitis C virus infection. METHODS: AT, MMP-1, MMP-3, and PAI-1 gene polymorphisms were analyzed by polymerase chain reaction in real time, whereas TGFB1 polymorphism was detected by polymerase chain reaction-based restriction fragment length polymorphism in 38 patients with established advanced liver fibrosis and 50 subjects from the general population. Grading of necroinflammation and staging of liver fibrosis were assessed by liver biopsy and graded according to modified histological activity index Ishak score. RESULTS: Regarding TGFB1 SNP, significant differences were found between G/G and G/C genotypes of patients with hepatic necroinflammation (P = 0.05) and hepatic fibrosis (P = 0.002). There were also significant differences among genotypes of patients with the AT SNP in hepatic necroinflammation (P = 0.01). The albumin-globulin ratio between genotypes of patients with the MMP-3 SNP gene showed significant differences (P = 0.02). CONCLUSION: Our findings demonstrate that a specific combination of genotypes associated with biochemical values and a histological high score determine more severe liver disease. The presence of the G/G genotype of TGFB1 SNP in patients was significantly associated with severity of liver necroinflammation and fibrosis. Patients with the G/G genotype of AT SNP were associated with severe necroinflammation. The albumin-globulin ratio was increased in patients with the 6A allele of MMP-3 SNP. These results might contribute to diagnosis and further establishment of liver disease treatment.