Analytical validation of an automated assay for the measurement of adenosine deaminase (ADA) and its isoenzymes in saliva and a pilot evaluation of their changes in patients with SARS-CoV-2 infection

Objectives The aim of the present study was to validate a commercially available automated assay for the measurement of total adenosine deaminase (tADA) and its isoenzymes (ADA1 and ADA2) in saliva in a fast and accurate way, and evaluate the possible changes of these analytes in individuals with SARS-CoV-2 infection. Methods The validation, in addition to the evaluation of precision and accuracy, included the analysis of the effects of the main procedures that are currently being used for SARS-CoV-2 inactivation in saliva and a pilot study to evaluate the possible changes in salivary tADA and isoenzymes in individuals infected with SARS-CoV-2. Results The automated assay proved to be accurate and precise, with intra- and inter-assay coefficients of variation below 8.2%, linearity under dilution linear regression with R2 close to 1, and recovery percentage between 80 and 120% in all cases. This assay was affected when the sample is treated with heat or SDS for virus inactivation but tolerated Triton X-100 and NP-40. Individuals with SARS-CoV-2 infection (n=71) and who recovered from infection (n=11) had higher mean values of activity of tADA and its isoenzymes than healthy individuals (n=35). Conclusions tADA and its isoenzymes ADA1 and ADA2 can be measured accurately and precisely in saliva samples in a rapid, economical, and reproducible way and can be analyzed after chemical inactivation with Triton X-100 and NP-40. Besides, the changes observed in tADA and isoenzymes in individuals with COVID-19 open the possibility of their potential use as non-invasive biomarkers in this disease

Brain-Sparing Sympathofacilitators Mitigate Obesity without Adverse Cardiovascular Effects.

Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PEGyAMPH) to exclude its central action. PEGyAMPH does not enter the brain and facilitates SNS activity via theβ2-adrenoceptor, protecting mice against obesity by increasing lipolysis and thermogenesis, coupled to higher heat dissipation, which acts as an energy sink to increase energy expenditure without altering food intake or locomotor activity. Thus, we provide proof-of-principle for a novel class of exclusively peripheral anti-obesity sympathofacilitators that are devoid of any cardiovascular and brain-related side effects

Diferencias clínicas y hematimétricas en pacientes con trombocitemia esencial y mutación para el gen de la calreticulina

Abstract [PB-090] Introducción: La identificación de la mutación somática en el gen CALR ha supuesto un avance diagnóstico en las neoplasias mieloproliferativas crónicas. Una cuarta parte de los pacientes (ptes) con trombocitemia esencial (TE) presenta dicha mutación, diferenciando dos variantes: la CALR tipo 1 (deleciones) y tipo 2 (inserciones). La TE mutada por CALR podría tratarse no solo de una entidad distinta a nivel molecular, sino también a nivel clínico-analítico. Métodos: Estudio descriptivo y prospectivo unicéntrico. Se incluyen 95 pacientes con TE diagnosticados en el Hospital Miguel Servet. Se analizan variables demográficas, características clínicas y hematimétricas en función de la biología molecular del paciente, establecimiento las diferencias observadas entre los pacientes con mutación JAK-2 y CALR (tipo 1 y tipo 2). Resultados: 35 eran hombres y 60 mujeres. Del total de pacientes, 55 presentaban la mutación JAK-2 (57, 89%), 22 la mutación CALR (23, 15%) (tipo 1: 12 ptes (46, 15%) y tipo 2: 10 ptes (38, 46%)), 5 la mutación MPL (5, 2%) y 9 eran triples negativos (9, 4%). Los ptes con TE mutada con CALR eran más jóvenes que los JAK-2, mediana de edad 65 años (29-84) y 72 años (40-96) respectivamente. Al diagnóstico, las cifras de hemoglobina y leucocitos en ptes JAK-2 eran superiores (mediana 14, 6 g/dL y 9, 30. 10³/µL) frente a CALR tipo 1 (mediana 14, 1 g/dL y 7, 78.10³/µL) y tipo 2 (14, 4 g/dL y 7, 80.10³/µL) y presentaban un recuento menor de plaquetas (mediana 744.10³/µL) frente a CALR tipo 1 (mediana 836. 10³/µL) y tipo 2 (mediana 916.10³/µL). Todos los pacientes CALR presentaban niveles normales de eritropoyetina mientras que un 18% JAK-2 presentaban niveles descendidos. 17 ptes (12, 72%) JAK-2, 3 ptes (25%) CALR tipo 1 y 1 pte (10%) CALR tipo 2 presentaban esplenomegalia. Presentaron episodio trombótico previo al diagnóstico: 5 ptes JAK- 2 (9%), de éstos 5 ptes eran hipertensos y 2 dislipémicos, 1 pte CALR tipo 1 (8, 3%), era hipertenso, dislipémico y fumador y ninguno CALR tipo 2, 1 pte era hipertenso. Tras el diagnóstico 1 pte JAK2 presentó nuevo episodio trombótico posteriormente. Al diagnóstico, 41 pacientes JAK-2 se les realizó biopsia ósea (74, 5%) con reticulina grado 1: 11 ptes (26, 82%), grado 2: 3 ptes (7, 3%) y grado 3: 0 ptes; a 11 ptes CALR tipo 1 (91, 6%) con reticulina grado 1: 3 ptes (27, 27%) y grado 2-3: 0 ptes; a 7 pacientes CALR tipo 2 (70%) con reticulina tipo 1: 3 ptes (44, 85%) y grado 2-3: 0 ptes. Conclusiones: La TE con mutación CALR parece comportarse de manera diferente en térmicos de características biológicas, hematológicas y clínicas frente a la mutación JAK2. Afecta a individuos relativamente jóvenes y se caracteriza por un recuento de plaquetas mayor pero con un riesgo trombótico inferior, especialmente los pacientes CALR tipo 2. Aunque en nuestra serie no encontramos grandes diferencias entre los subtipos de CALR, probablemente por el escaso número de ptes, creemos que ampliando la muestra existan diferencias entre ambos subgrupos que podrían implicar diferentes algoritmos terapéuticos

How Our Personality Shapes Our Interactions with Virtual Characters - Implications for Research and Development

Abstract. There is a general lack of awareness for the influence of users´ personality traits on human-agent-interaction (HAI). Numerous studies do not even consider explanatory variables like age and gender although they are easily accessible. The present study focuses on explaining the occurrence of social effects in HAI. Apart from the original manipulation of the study we assessed the users ́personality traits. Results show that participants ´ personality traits influenced their subjective feeling after the interaction, as well as their evaluation of the virtual character and their actual behavior. From the various personality traits those traits which relate to persistent behavioral patterns in social contact (agreeableness, extraversion, approach avoidance, self-efficacy in monitoring others, shyness, public self-consciousness) were found to be predictive, whereas other personality traits and gender and age did not affect the evaluation. Results suggest that personality traits are better predictors for the evaluation outcome than the actual behavior of the agent as it has been manipulated in the experiment. Implications for research on and development of virtual agents are discussed