Gender-Specific Fine Motor Skill Learning Is Impaired by Myelin-Targeted Neurofibromatosis Type 1 Gene Mutation.

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene. The clinical presentation of NF1 includes diverse neurological issues in pediatric and adult patients, ranging from learning disabilities, motor skill issues, and attention deficit disorder, to increased risk of depression and dementia. Preclinical research suggests that abnormal neuronal signaling mediates spatial learning and attention issues in NF1; however, drugs that improve phenotypes in models show inconclusive results in clinical trials, highlighting the need for a better understanding of NF1 pathophysiology and broader therapeutic options. Most NF1 patients show abnormalities in their brain white matter (WM) and myelin, and links with NF1 neuropathophysiology have been suggested; however, no current data can clearly support or refute this idea. We reported that myelin-targeted Nf1 mutation impacts oligodendrocyte signaling, myelin ultrastructure, WM connectivity, and sensory-motor behaviors in mice; however, any impact on learning and memory remains unknown. Here, we adapted a voluntary running test-the complex wheel (CW; a wheel with unevenly spaced rungs)-to delineate fine motor skill learning curves following induction of an Nf1 mutation in pre-existing myelinating cells (pNf1 mice). We found that pNf1 mutant females experience delayed or impaired learning in the CW, while proper learning in pNf1 males is predominantly disrupted; these phenotypes add complexity to the gender-dependent learning differences in the mouse strain used. No broad differences in memory of acquired CW skills were detected in any gender, but gene-dose effects were observed at the studied time points. Finally, nitric oxide signaling regulation differentially impacted learning in wild type (WT)/pNf1, male/female mice. Our results provide evidence for fine motor skill learning issues upon induction of an Nf1 mutation in mature myelinating cells. Together with previous connectivity, cellular, and molecular analyses, these results diversify the potential treatments for neurological issues in NF1.

[Overview of the interstitial lung disease in the Southeast of Mexico]. / Panorama de la enfermedad pulmonar intersticial en el sureste de México.

Background: Interstitial lung disease (ILD) corresponds to a heterogeneous group of pathologies that differ in etiology with common clinical and radiological manifestations. In Latin America and Mexico, reports are scarce and the need for studies to understand the scenario is emphasized. Objective: To analyze a multidimensional profile in patients with interstitial lung disease in Yucatan. Method: This is an observational, prospective, analytic, descriptive study including consecutive patients diagnosed with ILD over a 4-year period. Demographic and clinical data, lung function tests, chest imaging, serum immunological profile, and echocardiographic findings were recorded. Differences between subgroups were analyzed performing a one-way analysis of variance (ANOVA). Results: 110 patients were included. The median age was 60 years and women were most affected. The main cause of ILD was related with connective tissue diseases (CTD). A group subanalysis revealed that Idiopathic pulmonary fibrosis (IPF) was common in males with a history of smoking and an imaging pattern of usual interstitial pneumonia. Lung function tests showed a moderate-to-severe pulmonary restriction (FVC 55%p) and mild hypoxemia (PaO2 79mmHg). Positive antinuclear antibodies are less likely in cases with IPF (20 vs. 65%; p = 0.006). Conclusion: In Southeastern Mexico, ILD occurs in women in their seventh decade of life; the most common cause is related with CTD. Our results support that ILD has a heterogeneous expression and is relevant the need for subsequent studies characterizing each ILD.

Introducción: La enfermedad pulmonar intersticial (EPI) corresponde a un grupo heterogéneo de patologías que difieren en su etiología pero tienen manifestaciones clínicas y radiológicas comunes. En Latinoamérica y México los reportes son escasos, enfatizando la necesidad de estudios que permitan conocer su escenario clínico-epidemiológico. Objetivo: Realizar un análisis multidimensional y contrastado de la EPI en la población de la Península de Yucatán. Método: Estudio observacional, prospectivo, analítico y descriptivo, que incluye la totalidad de pacientes diagnosticados de EPI en un período de 4 años. Se registraron datos demográficos y clínicos, pruebas de función pulmonar, imagenología del tórax, perfil inmunológico y ecocardiografía transtorácica. Se analizaron las diferencias según la etiología mediante análisis de la varianza de una sola vía (ANOVA). Resultados: Se incluyeron 110 pacientes con una mediana de edad de 60 años y predominio del sexo femenino. La causa principal de la EPI fue relacionada con enfermedad del tejido conectivo. El subanálisis de grupos mostró que la fibrosis pulmonar idiopática (FPI) es frecuente en los varones con antecedente de tabaquismo y patrón tomográfico de neumonía intersticial usual. Las pruebas de función pulmonar demostraron restricción pulmonar moderadamente grave (FVC 55%p) e hipoxemia leve (PaO2 79 mmHg). La positividad de anticuerpos antinucleares ocurre en menor proporción en la FPI (20 vs. 65%, p = 0.006). Conclusiones: En el sureste de México, la EPI ocurre en mujeres de la séptima década de la vida y se relaciona con enfermedad del tejido conectivo. Nuestros resultados respaldan que la EPI tiene expresión heterogénea y se requieren estudios subsecuentes sobre cada tipo de enfermedad.

Obestatin signalling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4/KLF15 axis.

BACKGROUND: A therapeutic approach for the treatment of glucocorticoid-induced skeletal muscle atrophy should be based on the knowledge of the molecular mechanisms determining the unbalance between anabolic and catabolic processes and how to re-establish this balance. Here, we investigated whether the obestatin/GPR39 system, an autocrine signalling system acting on myogenesis and with anabolic effects on the skeletal muscle, could protect against chronic glucocorticoid-induced muscle atrophy. METHODS: In this study, we used an in vivo model of muscle atrophy induced by the synthetic glucocorticoid dexamethasone to examine the liaison molecules that define the interaction between the glucocorticoid receptor and the obestatin/GPR39 systems. The findings were extended to in vitro effects on human atrophy using human KM155C25 myotubes. RESULTS: KLF15 and FoxO transcription factors were identified as direct targets of obestatin signalling in the control of proteostasis in skeletal muscle. The KLF15-triggered gene expression program, including atrogenes and FoxOs, was regulated via KLF15 ubiquitination by the E3 ubiquitin ligase NEDD4. Additionally, a specific pattern of FoxO post-translational modification, including FoxO4 phosphorylation by Akt pathway, was critical in the regulation of the ubiquitin-proteasome system. The functional cooperativity between Akt and NEDD4 in the regulation of FoxO and KLF15 provides integrated cues to counteract muscle proteostasis and re-establish protein synthesis. CONCLUSIONS: The effective control of FoxO activity in response to glucocorticoid is critical to counteract muscle-related pathologies. These results highlight the potential of the obestatin/GPR39 system to fine-tune the effects of glucocorticoids on skeletal muscle wasting.

Validity of an Instrument to Detect Cheating Confirmed by the Elicited Emotional Reactions.

Cheating forms part of a complex emotional and cognitive process. However, although a relatively mundane phenomenon, instruments to evaluate cheating and its effects socially are scarce. This paper presents a five-stage approach aimed at providing validity to an instrument designed to assess cheating - specifically, its detection, and emotional reactions towards it once detected. An instrument was designed after (1) reviewing the relevant literature on cheating, in order to (2) design a bank of stimuli, (3) formulate a Delphi panel to judge the most coherent and pertinent ones, and (4) perform three pilot studies to adjust the final version of the instrument. Results from Stages 1 to 4 show that content validity was achieved for the Instrument for Detecting Cheating and its Emotional Reactions (INDETRAE, in Spanish: Instrumento para la Detección de Trampa y sus Reacciones Emocionales). Stimuli were grouped into five categories of 18 different scenarios, for a total of 90 vignettes: meaning, the INDETRAE is a 5-category, vignette-based questionnaire consisting of contrasting social cost-benefit scenarios, where the cheating situation affects an undefined, a first or a third person, and also a neutral category with no cheating. In Stage 5, several chi-squared tests (p < 0.0005) revealed significant differences between categories, proving that the instrument can indeed be used to detect cheating and to identify differentiated emotional reactions - for example, anger when there was detriment to a third person as opposed to neutral situations, or glad when there was a case of cheating which benefited the first person. The last stage counts as the first approximation to support construct validity of the INDETRAE. The most important contribution of this work consists in developing an instrument to detect cheating, confirmed by the resulting emotional reactions, which therefore demonstrate its validity.

Diseño de un dispositivo de asistencia ventilatoria temporal de lazo cerrado basado en bolsa válvula-mascarilla / Design of a closed-loop temporary ventilation assistance device based on bag valve mask

Desde inicios del 2020, el mundo se ha visto afectado por la COVID-19 causada por el SARS-CoV-2, que en agosto lo padecen más de 31 millones de pacientes, algunos de los cuales presentan el síndrome de distrés respiratorio, que requiere de ventilación mecánica. Por el alto número de contagios, la disponibilidad de ventiladores para el tratamiento es escasa. Se presenta la descripción de un prototipo de un dispositivo de asistencia ventilatoria temporal de lazo cerrado de bajo costo; el AR_CODEX, basado en una bolsa válvula-mascarilla (BVM), que contribuye al mantenimiento ventilatorio mínimo del paciente durante un tiempo corto en casos donde no hay disponibilidad de ventiladores mecánicos. Para esto, se diseñó y construyó un sistema mecánico ajustable que compresiona la bolsa de ventilación, el cual cuenta con sensores de flujo y presión. Además, se elaboró una interfaz gráfica para un adecuado monitoreo del paciente y un sistema de control para variables como volumen, presión máxima, frecuencia respiratoria y relación inspiración: espiración. Por otro lado, existe un problema de sensibilidad en el sensor de flujo debido a varios factores, como la variación del voltaje en los motores. Adicionalmente, la implementación de un lazo cerrado es importante para compensar variaciones aleatorias en el funcionamiento del dispositivo. Es necesario realizar pruebas en animales para evaluar el correcto funcionamiento de AR_CODEX en seres vivos.

In early 2020, the world has been affected from Covid-19 caused by SARS-CoV-2. By August there were more than 31 million patients, some of them suffering from respiratory distress that requires mechanical ventilation. Due to the rise of infection rates there is no ventilator availability for the treatment. In this work we describe a reduced cost closed loop temporal assisted ventilation device prototype, AR_CODEX. It is based on mask valve bag (BVM from its Spanish initials), contributing to the minimum ventilation maintenance for the patient du-ring a short period of time when there is no mechanical ventilation availability. For this purpose an adjustable mechanical system was designed and built to pressurize the ventilation bag that is equipped with flux and pres-sure sensors. Additionally a graphical interface was developed to include adequate monitoring and controlling system for volume, maximum pressure, respiratory frequency and inhalation/exhalation rate. In addition there is a sensibility issue on the flux sensor due to engine voltage variation. A closed loop implementation is important to overcome aleatory variations during the device operation. It is needed to run AR_CODEX device performance test on animals to evaluate prior to use it directly on human patients.

Solitary fibrous tumors of the pleura: a clinical-pathological characterization emphasizing changes in lung function.

Solitary fibrous tumors of the pleura (SFTP) represent less than 5% of all pleural tumors with a higher susceptibility for men in the sixth and seventh decades of life. Imaging and histopathological analyses indicate that these tumors have an unpredictable clinical course since larger tumors are often associated with malignancy; however, this assumption is not universal. In addition, there are no systematic descriptions of lung function in either the basal or post-surgical scenarios of SFTP patients. We describe a series of 3 patients between 4th and 5th decade of life with a benign histopathological SFTP without local recurrence in their follow-up. We also analyzed changes in lung function, emphasizing possible associations with clinical recovery.

Sustainable Accessibility: A Mobile App for Helping People with Disabilities to Search Accessible Shops.

People with motor disabilities must face many barriers and obstacles in their daily lives, making it difficult to perform everyday tasks. The purpose of this work is to improve their living conditions by providing an app with accessibility information in an updated, reliable and friendly form. The development of the system integrates national and regional accessibility regulations, architectural aspects, with an extensive field work, and a sustainable software process. The levels of accessibility and the requirements of the application are defined in the first phases of the project. The field work included the evaluation of 357 commercial establishments in the city of Murcia, Spain, showing that only 25% have a good accessibility, 40% are practicable with help, and 35% are inaccessible shops. The proposed system achieves its objectives of being sustainable and helping in the accessibility. Besides, the system can be a great incentive for businesses to improve their accessibility conditions. In conclusion, new technologies must have a much more active role in the promotion of universal accessibility. These tools must also consider the necessary requirements of sustainable development.

Manejo del empiema complicado con ventana torácica y sistema de presión negativa / Management of complicated empyema with thoracic window and negative pressure system

Introducción: El empiema torácico se define como derrame pleural purulento. La causa más frecuente es el infeccioso paraneumónico, sin embargo, puede presentarse en escenarios posquirúrgicos o postraumáticos. El empiema sigue una evolución progresiva trifásica y el tratamiento debe enfocarse a la causa de la enfermedad, fase evolutiva, y el estado general del paciente. Algunos casos requieren toracotomía con drenaje abierto tipo ventana torácica para solucionar el padecimiento. Materiales y Método: Estudio observacional, retrospectivo y descriptivo basado en una serie de casos. Se analizaron datos de pacientes consecutivos con empiema intervenidos con toracotomía con drenaje abierto tipo ventana torácica y uso de sistema de presión negativa en un Hospital de 3er Nivel del Sureste de México de octubre 2015 a junio 2017. Resultados: Se analizaron seis casos, la mediana de edad fue 46 años (rango intercuartílico 34-47) y 67% eran hombres. El sistema de presión negativa se colocó en el periodo posquirúrgico con una mediana de 6 días (rango intercuartílico 5-7). El tiempo medio de permanencia fue de 61 días (RIC 43-148). Finalmente, el tiempo de estancia hospitalaria fue de 72 días (RIC 49-87). El 67% de los casos evolucionó con cierre de la ventana torácica y adecuada expansión pulmonar. Conclusiones: En pacientes con empiema crónico, la terapia integral que incluya toracotomía con ventana torácica y el uso de sistema de presión negativa es una estrategia aceptable de tratamiento. Se requieren más estudios que ratifiquen los resultados de forma más objetiva.

Background: Thoracic empyema is defined as a purulent pleural effusion. Its most common origin is parapneumonic, nonetheless, post-surgical or post-traumatic empyema can also occur. Empyema has a progressive three-phase evolution and the treatment must focus to the evolutionary phase, cause of the disease and overall state of the patient. Some cases would undergo through thoracotomy with thoracic window open drainage to solve the disease. Material and Methods: This is an observational, retrospective and descriptive study based on all consecutive patients with empyema who underwent thoracotomy with thoracic window open drainage in a 3rd level hospital in the southeast of Mexico between october 2015 and june 2017. Results: We identified 6 cases. Median of age was 46 years (IQR 34-47) and 67% were male. The negative pressure system was placed in the 6th day of surgery (IQR 5-7). Median time of use was 61 days (IQR 43-148). Finally, the length of hospital stay was 72 days (IQR 49-87). 67% of the cases had chest window closure with adequate lung expansion. Conclusions: when we face a clinical scenario with chronic empyema, an integral therapy that includes thoracic window thoracotomy with a negative pressure system is an acceptable treatment strategy. Subsequent studies are required in order to ratify the results

Management of Complicated Empyema with Thoracic Window and Negative Pressure System

Introduction: the thoracic empyema is defined as a purulent pleural effusion. Its most frequent cause is infectious parapneumonic effusion; however, postsurgical or posttraumatic empyema can also occur. The empyema has a progressive three-phase evolution and its treatment shall focus on the cause of the disease, the evolutionary phase and the general condition of the patient. In order to cure this condition, some cases require thoracotomy with open thoracic window drainage. Materials and Method: observational, retrospective and descriptive study based on a series of cases. We analyzed data from consecutive patients with empyema who underwent thoracotomy with open thoracic window drainage and using a negative pressure system in a third-level care hospital in the southeast of Mexico between October 2015 and June 2017. Results: we analyzed 6 cases. Median of age was 46 years (interquartile range 34-47), and 67% were male. The negative pressure system was placed during the postsurgical period, with a median of 6 days (interquartile range 5-7). The mean permanence time was 61 days (IQR 43-148). Finally, the length of hospital stay was 72 days (IQR 49-87). 67% of the cases had thoracic window closure and adequate lung expansion. Conclusions: in patients with chronic empyema, an integral therapy including thoracic window thoracotomy with a negative pressure system is an acceptable treatment strategy. More studies are required in order to ratify the results more objectively.

Pérdida recurrente del embarazo e hipertensión pulmonar idiopática / Recurrent pregnancy loss and idiopatic pulmonary hypertension

Resumen La pérdida recurrente del embarazo ocurre cuando una mujer tiene 2 ó más pérdidas de embarazos clínicos antes de las 20 semanas de gestación. Existen múltiples factores de riesgo relacionados con este padecimiento, entre ellos, la presencia de Hipertensión Pulmonar (HP) se vincula con elevada mortalidad (30-56% de los casos) y riesgo de abortos entre las semanas 9 y 12 de gestación. No se conoce con precisión la frecuencia de asociación entre las condiciones clínicas referidas. Presentamos el caso de una mujer de 31 años de edad que ingresó al hospital con un aborto en evolución, en el periodo posterior al legrado evidencian Hipoxemia Grave e Insuficiencia Cardiaca Derecha; durante el abordaje diagnóstico se confirma que la causa primaria de la recurrencia de abortos se encuentra asociada con la presencia de Hipertensión Pulmonar Idiopática.

Abstract Recurrent pregnancy loss occurs whenever a woman has 2 or more miscarriages of their clinical pregnancy before 20 weeks of gestation. There are multiple risk factors relates to this condition, among, them, the presence of pulmonary hypertension (PH) is linked with high mortality (30-56% of cases) and risk of miscarriages between 9 weeks and 12 of gestation. The prevalence of both conditions are not well known. Here, we present the case of a 31 year-old women who was admitted to the hospital with an abortion in evolution, immediately after the curettage, the patient exhibit severe hypoxemia in association with Right Heart Failure; the medical approach established that the primary cause of recurrent abortions was an uncontrolled idiopathic pulmonary hypertension.

Síndrome de Hamman / Hamman syndrome

Resumen Se conoce como Síndrome de Hamman al neumomediastino espontáneo. Condición considerada benigna, autolimitada y poco reportada en la literatura nacional e internacional. Es probable que exista un subregistro o no se dé a conocer lo suficiente. Debe tenerse en cuenta en todo paciente joven que ingrese a los servicios de urgencias por dolor torácico, disnea y enfisema subcutáneo. El diagnóstico se realiza por sospecha clínica y se confirma con los rayos x de tórax. El tratamiento es netamente conservador. Presentamos un caso ilustrativo de esta condición que se presentó en un joven después de un episodio paroxístico de tos ocasionado por contacto con gasolina. Su condición previa era completamente normal. (Acta Med Colomb 2016; 41: 206-210).

Abstract Spontaneous pneumomediastinum is known as Hamman's syndrome. This condition is considered benign, self-limited and is little reported in the national and international literature. It is probably underreported or is not enough publicized. It must be considered in every young patient admitted to the emergency department with chest pain, dyspnea and subcutaneous emphysema. The diagnosis is made by clinical suspicion and is confirmed by chest X-rays. The treatment is clearly conservative. An illustrative case of this condition that occurred in a young man after a paroxysmal coughing episode caused by contact with gasoline is presented. Its previous condition was completely normal. (Acta Med Colomb 2016; 41: 206-210).

The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.