Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors.

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary.

Influence of taste sensitivity on preference and sensory perception of mezcal.

The perception of orosensory stimuli, which includes flavor, can vary between individuals. These individual variations in oral sensations can be due to genetic factors and it would appear that they can predict food liking and consumption. The most studied source of variation is related to bitter taste perception associated with 6-n-propylthiouracil (PROP) responsiveness. In this context, humans can be classified as non-tasters (NT), medium tasters (MT) and supertasters (ST). Evidence suggests that genetic variation in bitter taste perception contributes to differences in the level of irritation caused by alcohol perception in solutions. The aim of this investigation was to study the bitter taste sensitivity among a group of mezcal consumers and its relationship with sensory perception and preference through PROP taster status. The tests were carried out in the state of Oaxaca in Mexico. A total of 83 mezcal consumers were classified by their PROP taster status and were asked to provide sensory descriptors for five mezcal samples and rate them according to the level of liking. The three-solution test was used to classify the subjects as NT, MT, and ST, while a Multiple Factor Analysis (MFA) was used to visualize the sensory descriptors provided by these three groups. The proportion of MT subjects was 16%, while the proportion of NT and ST was 34 and 51%, respectively. The MT provided higher liking ratings for at least three mezcal samples. According to MFA, the mezcal samples were organized in a similar configuration along the two dimensions. However, NT mentioned a limited number of simple terms (strong flavor, tasteless, burning in the mouth) to describe the samples, whereas ST used a more complex vocabulary (astringent, smoky, scratchy aftertaste). These data suggest that the preference for mezcal samples was similar for non-taster and supertasters, but there are indications that the sensory perception of mezcal differs between groups.

La risa: niveles y factores demográficos, en el contexto de la COVID-19 / Laughter: demographic levels and factors, in the context of COVID-19

Introducción: La pandemia no se detiene, los estudios sobre la misma tampoco; esta pandemia produce dolor, tristeza, desesperación y muertes, cuyos números son incalculables. Ante esta situación difícil y dolorosa, la risa levanta su bandera de esperanza. Objetivo: El estudio tiene el objetivo de describir los niveles y los factores demográficos de la risa, en el contexto la COVID-19. Métodos: El estudio corresponde a un enfoque cuantitativo, de tipo descriptivo, de corte transversal. Los datos sobre los niveles de la risa se obtuvieron mediante una encuesta virtual, cuyos participantes fueron 101, de edades entre 20 y 60 años, quienes participaron voluntariamente, procedentes de las tres regiones del Perú: costa, sierra y selva. Los datos sobre la experiencia de la risa, con misma encuesta, con el tipo Likert: nunca, a veces y siempre. Resultados: De los 101 participantes, 87 (entre 20 y 60 años) presentan una risa en el nivel alto y 14 en el nivel medio. 14 participantes (entre solteros, casados, divorciados y convivientes) revelan una risa en el nivel medio y 87 en el nivel alto. De las tres regiones (costa, sierra y selva), 14 participantes se ubican en el nivel medio y 87 en el nivel alto. Por otro lado, 6 hombres y 8 mujeres practican una risa ubicada en el nivel medio, en el alto 28 y 59, respectivamente. En el factor: religión, 14 (entre católicos, adventistas, evangélicos y otros) revelan una sonrisa en el nivel medio, 87 en el alto. Según el factor: nivel de estudios (primario, secundario y superior), 14 y 87 ubican su risa en el nivel bajo y alto, respectivamente. En el círculo familiar y de los amigos, se experimenta siempre la risa: 58.4% y 66.3%, respectivamente; para los encuestados es más fácil reír, siempre, 54.5% y 66.3%, en el entorno familiar y de los amigos, respectivamente. Declararon que la risa previene las enfermedades, fortalece la salud, evita el covid-19, fortalece el sistema inmunológico y limita la producción de la hormona cortisol (responsable del estrés), siempre 70.3%, 31.7%, 81.2; 31.7%, 71.3% y 83.2%, respectivamente. Conclusión: En el contexto de la COVID-19, los niveles más significativos de la risa encontrados en el estudio son dos: medio y alto; los factores demográficos más ponderados son: edad, sexo, religión y estado laboral.

Introduction: The pandemic does not stop, neither does the studies on it; This pandemic produces pain, sadness, despair and deaths, the numbers of which are incalculable. Faced with this difficult and painful situation, laughter raises its flag of hope. Objective: The study aims to describe the levels and demographic factors of laughter, in the context of COVID-19. Methods: The study corresponds to a quantitative, descriptive, cross-sectional approach. The data were obtained through a virtual survey, whose participants were 101, from the three regions. Results: Of the 101 participants, 87 (between 20 and 60 years old) are located in the high level and 14 in the medium level. Similarly, 14 (among single, married, divorced and cohabitants) in the medium level and 87 in the high level. Of the three regions (coast, mountains and jungle), 14 in the medium level and 87 in the high level. On the other hand, 6 men and 8 women are in the medium level, in the high 28 and 59, respectively. In the factor: religion, 14 (among Catholics, Adventists, Evangelicals and others) in the medium level, 87 in the high. According to the factor: educational level (primary, secondary and higher), 14 and 87 are located in the low and high level, respectively. In the family and friends circle, laughter is always experienced: 58.4% and 66.3%, respectively; for respondents it is easier to laugh, always, 54.5% and 66.3%, in the family environment and with friends, respectively. They declared that laughter prevents diseases, strengthens health, prevents covid-19, strengthens the immune system and limits the production of the hormone cortisol (responsible for stress), always 70.3%, 31.7%, 81.2; 31.7%, 71.3% and 83.2%, respectively. Conclusion: In the context of COVID-19, the most significant levels of laughter found in the study are two: medium and high; the most weighted demographic factors are: age, sex, religion, and employment status.

Evaluación de la efectividad terapéutica y tolerabilidad del sulglicotide (demucineR) en pacientes con gastritis erosivas crónicas y duodenitis no erosiva (S199) / Evaluation of the effectiveness therapeutics and tolerance of sulglicotide (demucineR) in patients with gastritis erosiva chronic and duodenitis no erosiva (S199)

Se evaluó la efectividad e inocuidad de sulglicotide a la dosis de 200 mg tres veces al día durante 6 semanas en 62 pacientes con gastritis y duodenitis no lucerosa. Las evaluaciones fueron realizadas mediante examen clínico, endoscopia y opinión por parte del médico. A la sexta semana el tratamiento produjo una disminución significativa de los escores iniciales de todos los síntomas evaluados, así como en los escores endoscópicos. Los efectos adversos observados fueron: náuseas, resequedad, mal sabor y olor en la boca, cefalea, erupciones de la piel, mareos y sensación de hambre

Un bosquejo de la atencion de salud en Chile frente a las conclusiones de Alma Ata / An outline of the health care in Chile facing the Alma Ata conclusions

En Chile la historia del desarrollo de la atencion primaria es fundamentalmente la del consultorio urbano. A este respecto es sorprendente observar como la Declaracion de Alma Ata especifica la Atencion Primaria de Salud en terminos que coinciden total y absolutamente con el modelo y funcion del Consultorio Periferico Urbano desarrollado en Chile desde 1952 por el SNS y con especial enfasis a partir de la decada del 60. De este modo, puede verse un fenomeno de anticipacion historica en Chile dentro del devenir de la salud mundial orientada por la OMS. Esta anticipacion esta siendo evaluada por los autores del presente trabajo

Un bosquejo de la atencion de salud en Chile frente a las conclusiones de Alma Ata. / An outline of the health care in Chile facing the Alma Ata conclusions

En Chile la historia del desarrollo de la atencion primaria es fundamentalmente la del consultorio urbano. A este respecto es sorprendente observar como la Declaracion de Alma Ata especifica la Atencion Primaria de Salud en terminos que coinciden total y absolutamente con el modelo y funcion del Consultorio Periferico Urbano desarrollado en Chile desde 1952 por el SNS y con especial enfasis a partir de la decada del 60. De este modo, puede verse un fenomeno de anticipacion historica en Chile dentro del devenir de la salud mundial orientada por la OMS. Esta anticipacion esta siendo evaluada por los autores del presente trabajo