Sex differences regarding the impact of a standardized adaptation session in Colombian patients with obstructive sleep apnea and poor adherence to positive airway pressure devices / Diferencias por sexo respecto al impacto de una sesión de adaptación en pacientes colombianos con apnea obstructiva del sueño y mala adherencia a dispositivos de presión positiva

Abstract Introduction: Positive airway pressure (PAP) is the most effective treatment for obstructive sleep apnea (OSA) but adherence to this device is poor. The Sleep and Breathing Disorders Clinic of Fundación Neumológica Colombiana (FNC) has a standardized adaptation session (SAS) aimed at patients with difficulties in using PAP devices. Objective: To evaluate the impact of a SAS in short-term adherence to PAP therapy in patients with OSA, and to determine differences by sex. Materials and methods: Before-and-after single cohort study conducted in 40 people aged >18 years with an apnea-hypopnea index >15/hour and treated at the FNC, Bogotá D.C. (Colombia) between 2015 and 2017, who attended a SAS due to poor adherence to PAP therapy (defined as <4 hours use in 70% of nights). Data on the hours of use of the PAP device and the percentage of days in which it was used >4 hours were recorded before and after the intervention to evaluate changes in patients' adherence. Descriptive statistics were used for data analysis. The paired samples t-test was used for the comparison of variables before and after the intervention. Results: A significant increase was observed in PAP device use (1.8 hours, 95%CI: 1.3-2.3; p<0.001) and in the percentage of days it was used >4 hours (35.6%, 95%CI: 26.0-45.3; p<0.001). Among men, the increase was higher in both cases (2.3 hours, 95%CI: 1.7-2.9; p=0.029 and 47.8%, 95%CI: 32.9-62.8; p=0.029). Conclusion: The SAS offered by the FNC, which includes education strategies and the identification and solving of barriers hindering the use of PAP devices, significantly increased the hours of PAP device use and the percentage of days in which it was used >4 hours in the study population, particularly in men.

Resumen Introducción. La terapia de presión positiva en la vía aérea (PAP) es el tratamiento más efectivo de la apnea obstructiva del sueño (AOS); sin embargo, la adherencia no es óptima. La clínica de trastornos respiratorios del sueño de la Fundación Neumológica Colombiana (FNC) tiene una sesión de adaptación estandarizada (SAE) dirigida a pacientes con dificultades en el uso de equipo PAP. Objetivo. Evaluar el impacto de una SAE en la adherencia a corto plazo a la terapia de PAP en pacientes con AOS y determinar diferencias por sexo. Materiales y métodos. Estudio de cohorte única de antes y después realizado en 40 pacientes >18 años con un índice de apnea-hipopnea >15/hora atendidos en la FNC, en Bogotá D.C., Colombia, entre 2015 y 2017 y que asistieron a una SAE debido a una pobre adherencia a la terapia de PAP (<4 horas de uso el 70% de las noches). Se registraron los datos de uso en horas del equipo de PAP y el porcentaje de días en que se usó más de 4 horas antes y después de la intervención. Los datos se analizaron mediante estadística descriptiva y se empleó la prueba T de muestras emparejadas para comparar las variables antes y después de la intervención. Resultados. Se observó un aumento significativo después de la SAE en las horas de uso del equipo de PAP (1.8 horas, IC95%: 1.3-2.3; p<0.001) y del porcentaje de días en que su uso fue >4 horas (35.6%, IC95%: 26.0-45.3; p<0.001); el incremento fue mayor en los hombres en ambos casos (2.3 horas, IC95%: 1.7-2.9; p=0.029, y 47.8%, IC95%: 32.9-62.8; p=0.029). Conclusión. La SAE que brinda la FNC, la cual incluye estrategias educativas y la identificación y solución de barreras que dificultan el uso del equipo de PAP, aumentó de forma significativa las horas de uso de los dispositivos de PAP y el porcentaje de días con uso >4 horas en la población de estudio, en particular en los hombres.

Molecular cloning and biochemical characterization of the first Na(+)-channel α-type toxin peptide (Acra4) from Androctonus crassicauda scorpion venom.

Due to the medical importance played in Turkey by stings of the scorpion Androctonus crassicauda, its venom has been studied with more attention. In this communication we report a new toxic peptide, named Acra4, because it is the fourth peptide completely characterized from venom of this scorpion. The peptide contains 64 amino acid residues stabilized by four disulfide bridges, with a molecular weight of 6937 Da. Purification of the lethal peptide was performed by three steps of high performance liquid chromatography (HPLC) separations, and the molecular weight was determined by mass spectrometry analysis and the full amino acid sequence was obtained by direct Edman degradation in conjunction with gene cloning. The LD50 of Acra4 was 50.5 ng/20 g mouse body weight (95% confidence intervals from 48.8 to 52.2 ng/20 g mouse body weight). Additionally, from a sample of cDNA of A. crassicauda four genes were cloned displaying sequence similarities to known scorpion toxins, and are reported here as potentially toxic peptides, named Acra5 to Acra8. Electrophysiological studies of Acra4 were performed using Na(+)-channels expressed in F11 cell culture, by patch-clamp recordings. This is the first time that such peptide from A. crassicauda having a specific Na(+)-channel α-type effect is reported. Its affinity toward Na(+)-channels in F11 cell line is in the order of 1 µM concentration.

New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing.

Scorpion venoms are a rich source of K(+) channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an α-helical segment to the C-terminal strand of a double- or triple-stranded ß-sheet, conforming a cystine-stabilized α/ß scaffold (CSα/ß). Here we show that two K(+) channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CSα/ß scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds.